Duet between sugars and hormones: The molecular dialogue fine‐tuning hypoxia acclimation in plants

ABSTRACT

Hypoxic conditions caused by submergence or soil waterlogging constrain plant growth and productivity. To survive, plants coordinately reprogram both sugar metabolism and phytohormone signaling to trigger adaptive responses; yet, the integrative regulatory frameworks governing this interaction remain unresolved. Here, we synthesize current knowledge on how sugars, acting as both metabolites and signals, intersect with phytohormone networks to regulate growth and survival under low‐oxygen stress. Under hypoxia, ethylene and auxin reshape root architecture, while cytokinin mediates sugar‐dependent regulation of shoot branching to optimize resource allocation. The dynamic interplay between abscisic acid and sugars is central to maintaining energy balance under cyclic day–night hypoxia. This interaction modulates the stomatal aperture, facilitates controlled starch degradation, and coordinates sucrose transport to sustain metabolism. Furthermore, crosstalk between primary sugars, gibberellin, and brassinosteroid fine‐tunes critical developmental transitions, including seed germination and internode elongation. Although individual signaling pathways under hypoxia have been well studied, their integration via sugar–hormone crosstalk remains elusive. To address these issues, we propose integrating synthetic low‐oxygen sensors that initially detect hypoxic stress with engineered sugar–hormone balancing circuits that subsequently fine‐tune metabolic and hormonal responses, thereby creating closed‐loop feedback systems for adaptive stress resilience. Such systems could enable “Sensing, Metabolism, Adaptation, and Regulation Technology” (SMART) crops to autonomously sense and adapt to hypoxia stress. By synthesizing current knowledge and existing gaps, our work proposes future directions to advance the development of hypoxia‐resilient crops through optimizing growth and yield stability under stress.

Sugar–hormone crosstalk enables plants to maintain metabolism and adjust development under low‐oxygen conditions. This review highlights how sugar metabolism and phytohormone signaling coordinate adaptive responses to hypoxia, identifies key knowledge gaps, and outlines future research directions for developing crops resilient to submergence and waterlogging stress.

INTRODUCTION

Over the last few decades, global warming‐induced climatic changes have increased the frequency and severity of prolonged waterlogging events worldwide (Jiang et al., 2025a). These conditions trigger oxygen deficiency (hypoxia or anoxia) in soils—a crucial abiotic stress that impairs genetic circuits and ultimately threatens crop productivity (Bailey‐Serres and Voesenek, 2008). Confronted with such challenging conditions, sessile plants have developed complex metabolic and signaling networks to sense and deal with low oxygen (Bailey‐Serres and Voesenek, 2008; Veen et al., 2025). The core of hypoxia adaptation lies in the dynamic interplay between sugars and phytohormones, which function as integrative molecular signals that translate environmental cues into coordinated physiological responses (Asim et al., 2023; Fabregas et al., 2026; Wang et al., 2025a). Despite increasing recognition of their individual roles, the mechanistic basis of sugar–hormone crosstalk under low‐oxygen stress remains fragmented, particularly in linking local sensing to whole‐plant acclimation. In this review, we integrate current knowledge on how specific sugars interact with key hormonal pathways to regulate hypoxia responses, with an emphasis on their coordinated roles in signal perception to whole‐plant acclimation.

Sugars play a dual role in plants, functioning not only as energy sources but also as key signaling molecules (Sanclemente et al., 2021; Lepper et al., 2025). Beyond metabolism, they regulate adaptive responses to stress by modulating gene expression, cellular homeostasis, and source–sink dynamics, that is, the allocation and redistribution of photo‐assimilates between producing (source) and consuming (sink) tissues (Veen et al., 2025; Wang et al., 2025b). Central to this sugar‐signaling framework are four key regulators—hexokinase (HXK), trehalose‐6‐phosphate (Tre6P), SNF1‐related kinase 1 (SnRK1), and target of rapamycin (TOR)—which act as energy sensors and integrators (Li and Zhao, 2024; Morales‐Herrera et al., 2023, 2024); often likened to “musketeers” guarding cellular energy, they coordinately balance growth and stress responses under fluctuating conditions (Herfurth et al., 2026). This signaling network operates in close coordination with hormonal pathways to fine‐tune plant growth and stress responses (Fàbregas et al., 2026; Supriya et al., 2025). Interactions between sugars and major phytohormones, including ethylene (ET), auxin (IAA), abscisic acid (ABA), cytokinin (CK), gibberellin (GA), and strigolactone (SL), have been widely reported under diverse abiotic stresses (León and Sheen, 2003; Ljung et al., 2015; Fàbregas et al., 2026).

Under low‐oxygen conditions, this sugar–hormone regulatory network is extensively reprogrammed, resulting in coordinated changes in hormonal homeostasis and carbohydrate metabolism. Consequently, the accumulation of ET, ABA, IAA, and specific sugars drives architectural remodeling as an adaptive escape strategy in several species, including Prunus persica (Ateeq et al., 2023, 2025), Cucumis sativus (Qi et al., 2020), and Vitis vinifera (Ge et al., 2024). The antagonistic relationship between sugars and SLs is exemplified in Oryza sativa, where sugar availability attenuates SL‐induced senescence, revealing an important layer of metabolic–hormonal crosstalk (Barbier et al., 2023). Although multi‐omics approaches have begun to uncover components of this network, direct molecular links between sugar signaling, hormone crosstalk, and plant hypoxia acclimation remain fragmented. Addressing this gap is critical for understanding how roots, as the primary sites of low oxygen perception, integrate local oxygen‐sensing signals with whole‐plant energy balance and developmental plasticity under stress. Insights into these mechanisms will not only enhance our understanding of plant adaptation to hypoxia but also support efforts to improve stress tolerance, stabilize yields, and develop SMART crops for increasingly variable environments (Palmgren and Shabala, 2024; Lavilla‐Puerta and Giuntoli, 2025; Raza et al., 2025). Accordingly, this review integrates emerging insights into sugar–hormone interactions during low‐oxygen stress and outlines mechanistic frameworks to guide efforts aimed at enhancing plant resilience to waterlogging and submergence.

TRANSITION OF SUGARS FROM METABOLIC FUEL TO STRESS SIGNALING UNDER HYPOXIA

Hypoxic or anoxic conditions induce a severe energy crisis by restricting O₂ availability and impairing mitochondrial respiration (Wagner et al., 2018). This leads to a rapid decline in ATP production and the collapse of phosphorylation‐dependent processes, further exacerbated by reduced photosynthesis (Bailey‐Serres and Voesenek, 2008; Veen et al., 2025). The severity of carbohydrate depletion depends on the developmental stage, pre‐stress conditions, and stress duration (Cho et al., 2021). The critical role of glycolytic energy maintenance is underscored by findings that partial defoliation—which limits carbohydrate translocation to roots—markedly increases hypoxia sensitivity (Bailey‐Serres and Voesenek, 2008; Supriya et al., 2025). To counteract these challenges, plants have evolved sophisticated mechanisms to sense energy status and key sugar metabolites (e.g., glucose, sucrose, and Tre6P) through the action of SnRK1 and TOR—two conserved protein kinases—ensuring metabolic adaptability and survival (Fàbregas et al., 2026).

Energy starvation and sugar signaling mechanisms

Under hypoxia, plants rely on glycolysis and fermentation for ATP production, accompanied by anaerobic metabolite accumulation (Bailey‐Serres and Voesenek, 2008; Veen et al., 2025). This metabolic reprogramming reduces sucrose export from source to sink tissues (Koch, 2004) and triggers anaerobic genes (e.g., alcohol dehydrogenases, ADH; lactate dehydrogenase, LDH; and pyruvate decarboxylase, PDC) alongside antioxidant defenses (Bailey‐Serres et al., 2012; Ateeq et al., 2023). Genetic evidence underscores sucrose synthase as critical, since Arabidopsis mutants lacking it show heightened hypoxia susceptibility (Bailey‐Serres et al., 2012; Santaniello et al., 2014). Conversely, sucrose availability enhances tolerance by stabilizing anaerobic genes and heat shock proteins (Loreti et al., 2018). Notably, O. sativa, which is considered as the most hypoxia‐tolerant crop, supports anaerobic germination via efficient starch degradation—a trait absent in most cereals (Perata et al., 1992, 1997). Together, these challenges engage a complex signaling network integrating transcriptional and metabolic responses to low oxygen.

Further, SnRK1 acts as a central energy deprivation sensor activated under hypoxia, where it regulates anaerobic genes such as ADH and PDC, and kinase‐inactive mutants display hypersensitivity to submergence in Arabidopsis and O. sativa (Cho et al., 2016, 2021). Mechanistically, SnRK1 forms complexes with regulatory subunits to phosphorylate key metabolic enzymes including sucrose phosphate synthase, trehalose‐6‐phosphate synthase, and fructose‐2,6‐bisphosphate kinase, thereby redirecting carbon flux toward catabolic pathways (Baena‐González and Lunn, 2020; Fichtner and Lunn, 2021). SnRK1 also interacts with basic leucine zipper 63 (bZIP63) to activate the starvation‐responsive gene (Dark‐Inducible 6; DIN6), linking energy deprivation to nitrogen metabolism (Mair et al., 2015). The induction of DIN6 under energy limitation and its association with RELATED TO AP (RAP) 2.12 (RAP2.12) mutants further suggest integration with amino acid metabolism during stress (Loreti et al., 2018).

Importantly, SnRK1 connects energy signaling with hypoxia responses through the SnRK1–RAP2.4h–PIP2 module, which coordinates the trade‐off between growth and hypoxia tolerance in plants (Liao et al., 2026). This module provides a regulatory interface linking metabolic status with oxygen deprivation signaling to fine‐tune survival and growth decisions under stress. Transcriptomic overlap between SnRK1 targets and hypoxia‐responsive genes further supports this connection, although sugar‐supplemented experimental systems may partially alter the transcriptional signatures associated with energy deprivation (Jardine and McDowell, 2023; Veen et al., 2025). Furthermore, the role of SnRK1 is developmentally specific, as overexpression of SNF1‐related protein kinase 1 catalytic subunit 10 (KIN10) interacts with RAP2.4 h, conferring submergence tolerance and modulating carbon and nitrogen metabolism in Arabidopsis (Tsai and Gazzarrini, 2012; Han et al., 2024; Liao et al., 2026). This age‐dependent regulation is linked to AMP/ATP imbalance under hypoxia, triggering autophagy and catabolic reprogramming, although tolerance is constrained by carbohydrate availability during submergence (Cho et al., 2021; Veen et al., 2024).

In contrast, TOR acts as a growth‐promoting kinase activated under nutrient sufficiency, but rapidly inhibited under energy deprivation (Baena‐González, 2010; Li and Zhao, 2024) and hypoxia (Kunkowska et al., 2023). TOR integrates oxygen and sugar signals by regulating the stability of ERFVII transcription factors, thereby linking metabolic status with hypoxia signaling. Under low oxygen, ATP depletion suppresses TOR activity, stabilizing ERFVII proteins and enabling hypoxia‐responsive gene expression (Kunkowska et al., 2023). Genetic and proteomic evidence shows that TOR is required for proper induction of hypoxia‐responsive genes, likely through phosphorylation of RAP2.12 regulatory domains (Mallén‐Ponce et al., 2022). Submergence‐induced ATP depletion therefore acts as a primary trigger for TOR inactivation, similar to prolonged darkness, where carbohydrate starvation suppresses TOR signaling (Loreti et al., 2018; Xiao et al., 2024). TOR suppression is accompanied by metabolic shifts, including fermentation activation and redox balancing through ethanol and acetaldehyde metabolism (Drew, 1997; Cho et al., 2021). In photosynthetic tissues, glucose‐derived signaling via glycolysis and mitochondrial metabolism activates TOR to promote root growth and transcriptional reprogramming, particularly through phosphorylation of E2F transcription factor a (E2Fa) in the Glc–TOR–E2Fa module (Xiong et al., 2013; Li and Zhao, 2024). Importantly, glucose signaling is indispensable for sustaining growth, as hormonal or external sugar supplementation cannot fully substitute photosynthetic carbon supply. Together, these findings identify TOR as a key integrator of sugar–energy signals controlling hypoxia responses, growth, and metabolism. Interaction with SnRK1 maintains energy balance and stress adaptation. Future studies should resolve upstream regulation and assess the Glc–TOR–E2Fa module for improving crop resilience and yield.

Carbohydrate degradation, transport, and source–sink dynamics

Sucrose and starch breakdown become critical for fueling glycolysis, and sucrose catabolism proceeds through two primary routes under hypoxia (Santaniello et al., 2014). The first one is the sucrose synthase pathway that produces fructose and UDP‐glucose, which are sequentially converted into glucose‐1‐phosphate (via UDP‐glucose pyrophosphorylase) and glucose‐6‐phosphate (via phosphoglucomutase) (Cho et al., 2021). Fructose then further phosphorylated by fructokinase to fructose‐6‐phosphate, maintaining glycolytic flux (Fagerstedt et al., 2024). The second one is the invertase pathway that hydrolyzes sucrose into fructose and glucose, which are then phosphorylated by fructokinase and HXK, respectively, at the cost of ATP/UDP (Fagerstedt et al., 2024). During oxygen deprivation, plants rely on glycolytic breakdown of carbohydrate reserves to sustain energy via fermentation, with species‐specific survival limits observed in Zea mays and Sorghum bicolor (Renziehausen et al., 2025; Zafar and Bailey‐Serres, 2025). The sucrose synthase pathway is energetically advantageous because of its low ATP requirement, generating fructose‐6‐phosphate and UDP‐glucose to support glycolysis and cell wall biosynthesis under hypoxia (Santaniello et al., 2014; Ateeq et al., 2025). However, hypoxia tolerance of Arabidopsis sus1/4 mutants through compensatory invertase activity highlights substantial metabolic redundancy in sugar utilization pathways (Yao et al., 2020). Consequently, sucrose synthase‐dependent ethanol fermentation appears to become critical primarily under combined oxygen and carbohydrate limitation (Jardine and McDowell, 2023). Furthermore, plants also accumulate alanine and gamma‐aminobutyric acid to maintain pH homeostasis and conserve carbon and nitrogen reserves (Wu et al., 2021). Alanine aminotransferase converts pyruvate and glutamate into alanine and 2‐oxoglutarate, thereby preventing pyruvate overaccumulation and supporting metabolic recovery upon reoxygenation (Fagerstedt et al., 2024; Asim et al., 2025). Simultaneously, glutamate decarboxylase‐mediated gamma‐aminobutyric acid production alleviates cytosolic acidification while preserving nitrogen for post‐stress recovery (Selinski et al., 2024).

Wetland plants tolerate hypoxia by mobilizing starch reserves to support shoot elongation, thereby enabling oxygen access through the low‐oxygen escape strategy (Akman et al., 2012; Loreti et al., 2018). Efficient anaerobic ATP production depends on a steady glucose supply. Starch is a key energy reserve under low oxygen in both cereals and Arabidopsis. However, O. sativa uniquely uses α‐amylase to break down starch for anaerobic germination—a trait absent in other cereals (Sanclemente et al., 2021). In contrast, Arabidopsis relies on different pathways to use starch during submergence (Veen et al., 2025). Unexpectedly, transcriptional attenuation of hypoxia responsive genes (HRGs) under sugar starvation in Arabidopsis unveils an oxygen–glucose crosstalk mechanism that prioritizes carbon availability over canonical hypoxia signaling (Triozzi et al., 2024). Concerning metabolic prioritization, the SnRK1–Tre6P regulatory axis acts as a key integrator of energy status. Supporting this hypothesis, hypoxia induces trehalose 6‐phosphate phosphatase (OsTPP7), reducing Tre6P levels and thereby relieving repression of SnRK1A in O. sativa. Activated SnRK1A triggers α‐amylase‐mediated starch degradation to ensure glycolytic substrate supply—representing a critical metabolic checkpoint for sustaining energy production under low oxygen (Lee et al., 2009; Jardine and McDowell, 2023).

Moreover, genetic dissection of CBL‐interacting protein kinase 15, a key component of the SnRK1 signaling pathway, underscores its importance in maintaining starch‐to‐sugar conversion across developmental stages (Cho et al., 2021). Plants maintain energy homeostasis under hypoxia by dynamically regulating carbohydrate metabolism, transport, and canopy photosynthesis to sustain carbon supply (Barreto et al., 2022). However, adaptive strategies vary among species and genotypes. Tolerant O. sativa cultivars accumulate greater nonstructural carbohydrate reserves than susceptible genotypes (Jardine and McDowell, 2023), whereas Mentha piperita conserves carbohydrate reserves during stress, while M. arvensis preferentially mobilizes them to sustain escape‐driven growth (Phukan et al., 2018). Collectively, these findings highlight efficient carbohydrate allocation and transport as critical determinants of waterlogging tolerance (Mignolli et al., 2021; Wang et al., 2025b). Nevertheless, the spatiotemporal coordination between catabolic starch degradation and concurrent anabolic processes remains poorly understood. This gap highlights the need to unravel tissue‐specific regulation of sugar transporters.

In addition, multiple transporter proteins—including those for transporting sorbitol (SOTs), sucrose (SUTs and SWEETs), and monosaccharides (MSTs)—coordinate carbohydrate redistribution across cellular compartments to mitigate energy shortages under stress (Mignolli et al., 2021; Asim et al., 2025; Wang et al., 2025b). This transport machinery facilitates the bidirectional movement of sucrose and sorbitol along concentration gradients (Salvi et al., 2022), particularly toward hypoxic root tissues, thereby sustaining anaerobic respiration and ATP production (Phukan et al., 2018). Compatible grafting preserves carbohydrate signaling and transport between rootstock and scion; disruptions impair carbon allocation and tree survival under waterlogging (Bhatt et al., 2015; da Silva et al., 2025). A mechanistic example of this principle was seen in waterlogging‐tolerant transgenic Arabidopsis, where enhanced expression of AtSWEET10 (regulated by RAP2/4) facilitates carbohydrate translocation to sink organs. This targeted mobilization of sugars supports root function and stress resilience, highlighting the broader role of sugar transport in maintaining carbon balance under hypoxic conditions (Phukan et al., 2016). Related studies in Prunus rootstocks have identified the sorbitol transporter gene SOT1 as hypoxia‐responsive, enabling sorbitol‐mediated carbon shuttling to oxygen‐deprived roots and indicating a conserved adaptative mechanism in woody perennials (Pistelli et al., 2012; da Silva et al., 2025). Collectively, these investigations support a model in which coordinated regulation of sugar transporters and metabolic pathways establishes a dynamic source–sink network that prioritizes carbon allocation to hypoxic tissues. In this framework, transporter activity, hormonal signaling, and metabolic reprogramming operate in an integrated manner to sustain energy homeostasis and root viability under oxygen limitation. However, critical gaps in our understanding remain regarding how these processes are coordinated over long distances in fruit trees. Addressing these challenges will benefit from integrative approaches, including metabolic engineering and synthetic biology, to redesign carbon partitioning networks and improve hypoxia tolerance in crops.

HORMONAL CONTROL OF HYPOXIA‐ADAPTED PLANTS

Plant hormones, derived from key metabolic pathways, act as signaling messengers that integrate local and systemic stress responses (Yuan et al., 2023; Asim et al., 2025; Renziehausen et al., 2025; Ashraf et al., 2026). Classical hormones, including ET, IAA, GA, ABA, and CK, together with emerging regulators including melatonin, brassinosteroid (BR), SL, and jasmonic acid (JA), collectively coordinate plant growth and stress adaptation (Barbier et al., 2023; Eerdekens et al., 2025; Munné‐Bosch, 2025). Under hypoxia, this hormonal network regulates adaptive traits such as aerenchyma formation, root architectural remodeling, and metabolic reprogramming. ET accumulation represents a key early event in low‐oxygen responses, amplifying downstream signaling and coordinating adaptive processes (Licausi et al., 2010, 2011; Sasidharan and Voesenek, 2015; Hartman et al., 2019; Zhao et al., 2021; Ashraf et al., 2026). This ET‐driven framework integrates IAA‐mediated root plasticity and ABA‐dependent metabolic adjustment, thereby enhancing survival under oxygen limitation (Zhou et al., 2020; Daniel and Hartman, 2024). In parallel, antagonistic interactions between GA and CK fine‐tune growth restraint and resource allocation to maintain energy balance, while additional crosstalk between IAA, CK, and tryptophan‐derived metabolites further refines root system architecture and stress adaptation (Tessi et al., 2023; Marash et al., 2024; Supriya et al., 2025; Wang et al., 2025c).

Across angiosperms, conserved, yet species‐specific hormonal crosstalk—centrally involving ET and IAA—coordinates hypoxia adaptation by regulating gene expression and developmental reprogramming for belowground resilience (Gobena et al., 2025; Ashraf et al., 2026). In Arabidopsis, hypoxia stabilizes ERFVIIs by inhibiting plant cysteine oxidase (PCO)‐mediated activation of the N‐end rule pathway (Gibbs et al., 2011; Weits et al., 2014; Zubrycka et al., 2023). This stabilization indirectly reshapes IAA signaling outputs, including auxin response factor (ARF)‐mediated transcriptional programs, thereby promoting adaptive traits such as lateral root emergence and directional root growth (Eysholdt‐Derzsó and Sauter, 2017; Renziehausen et al., 2025). Similar hormonal frameworks operate in crops such as O. sativa, where ET and IAA co‐regulate key transcripts—including 1‐aminocyclopropane‐1‐carboxylic acid synthase (ACS), 1‐aminocyclopropane‐1‐carboxylic acid oxidase (ACO), transport inhibitor response 1 (TIR1), and WUSCHEL‐related homeobox 11 (WOX11)—to induce adventitious root formation and hypocotyl elongation, key traits for flooding tolerance (Yamauchi et al., 2019). A more complex interplay between ET, IAA, and JA activates biosynthetic and signaling genes—including YUCCA that encodes flavin‐containing monooxygenases, PIN‐FORMED (PIN), lipoxygenase (LOX), and jasmonate‐resistant 1 (JAR1)—to induce aerenchyma and adventitious roots in Triticum aestivum (Nguyen et al., 2018).

Further, Z. mays shows JA–IAA coordination through Phytoglobin 1, supporting stem cell renewal under oxygen deficiency (Rathnayaka et al., 2023). These regulatory themes extend to horticultural species like Solanum lycopersicum (Eerdekens et al., 2025) and C. sativus (Qi et al., 2020). In fact, flooding triggers ET–IAA pathways through ACS and ACO isoforms and IAA transporters, promoting adventitious rooting. Similarly, waterlogging activates IAA and JA biosynthetic genes (tryptophan aminotransferase of Arabidopsis 1, TAA1; YUCCA; allene oxide cyclase, AOC; and allene oxide synthase, AOS), facilitating lateral root initiation (Ateeq et al., 2023; Ashraf et al., 2026). Under hypoxia, GA signaling is generally suppressed to conserve energy, stabilizing DELLA proteins that promote hypoxia‐responsive genes like ADH and PDC, enhancing survival in Arabidopsis (Robil et al., 2025). In contrast, deepwater rice uses an escape strategy where ET accumulation stabilizes SNORKEL1/2, triggering GA biosynthesis and rapid internode elongation to restore access to oxygen (Qin et al., 2022). In addition, CK signaling is often downregulated under low oxygen, and mutants with reduced CK levels show enhanced tolerance, as resources are redirected from shoot growth to anaerobic metabolism (Eerdekens et al., 2024).

Beyond classical hormones, emerging regulators such as melatonin and SL have been implicated in plant adaptive responses to low‐oxygen stress. Recent evidence identifies melatonin as a key regulator of hypoxia tolerance across diverse species (Jahan et al., 2025). Mechanistically, melatonin enhances stress resilience by reinforcing ROS‐scavenging systems, including superoxide dismutase, catalase, and ascorbate peroxidase, while preserving mitochondrial function and aerobic respiration (Zheng et al., 2017). In S. lycopersicum, exogenous melatonin sustains photosynthesis and redox homeostasis under stress (Jahan et al., 2024). Additionally, melatonin modulates ethylene and polyamine metabolism through repression of ACS, ACO, and ERFVIIs, and regulates chlorophyll‐associated gene expression to maintain photochemical efficiency (F_v /F_m ) (Zhang et al., 2019; Gu et al., 2021). It further fine‐tunes hypoxia signaling via ERF‐dependent transcriptional networks and calcium‐related signaling components, including calcineurin B‐like proteins and protein kinases, thereby integrating redox and stress signaling pathways (Luo et al., 2024; Park, 2024).

In contrast, the role of SL in hypoxia responses is still emerging. SL, carotenoid‐derived phytohormones, regulate plant architecture, including shoot branching, root development, and senescence (Barbier et al., 2023; Su and Xue, 2025). Under flooding conditions, SL have been suggested to contribute to recovery processes by interacting with ET and ABA signaling, particularly in promoting root regeneration and cellular reorganization, such as microtubule dynamics in V. vinifera (Ge et al., 2024). At the molecular level, SL signaling components such as SMAX1‐like proteins modulate downstream developmental responses, although their direct roles in hypoxia signaling remain to be fully elucidated. SL‐mediated regulation of IAA transport, nutrient signaling, and nitric oxide crosstalk may further contribute to adaptive root system remodeling under oxygen‐limited conditions (Kapulnik and Koltai, 2014; Sanchez‐Corrionero et al., 2023). Together, these findings suggest that while melatonin operates through well‐defined redox and transcriptional mechanisms, SL likely contribute to hypoxia adaptation through integrative hormonal crosstalk and developmental plasticity.

THE REGULATORY NETWORK UNDERLYING SUGAR–HORMONE CROSSTALK DURING HYPOXIA RESPONSES

Sugar–hormone crosstalk integrates metabolic and signaling networks to coordinate plant growth, energy homeostasis, and stress adaptation under hypoxia (Figure 1; Renziehausen et al., 2025). Extensive studies across diverse species have highlighted the essential roles of sugars, phytohormones, and their transport systems in mediating developmental and physiological acclimation to hypoxic stress (Gill et al., 2018; Fàbregas and Fernie, 2022; Fàbregas et al., 2026). Despite substantial progress in understanding individual sugar and hormone signaling pathways, the mechanisms by which these regulatory networks integrate across tissues, organs, and developmental stages under hypoxia remain poorly resolved. Deciphering how these processes are coordinated will be critical for understanding plant adaptive strategies and improving stress resilience.

Figure 1.

A conceptual model shows how central sugar metabolites integrate into key phytohormone biosynthesis and their dynamic interactions across progressive hypoxia stages

(A) Dynamics of primary sugars and hormonal signals coordinating hypoxia survival and recovery strategies. During hypoxia, glucose, fructose, and ethylene (ET) levels show a modest increase at the initial stage, followed by a marked reduction as the stress progresses. By contrast, sucrose, trehalose 6‐phosphate (Tre6P), auxin (IAA), and cytokinins (CK) remain low during long‐term hypoxia. Following reoxygenation, the concentrations of all phytohormones and primary sugars show multiple bursts relative to their baseline levels at various time points (Veen et al., 2025; Wang et al., 2025a). (B) All phytohormones are ultimately derived from primary metabolic precursors, highlighting the close connection between fundamental metabolic pathways and the biosynthesis of signaling molecules that regulate plant growth and development (Fàbregas and Fernie, 2021; Supriya et al., 2025). IAA and ET are synthesized from amino acid‐derived intermediates, with both Trp‐dependent and ‐independent IAA pathways utilizing PEP from glycolysis as a shared precursor. ET biosynthesis originates from methionine through a two‐step conversion: S‐adenosyl‐L‐methionine (SAM) synthesis, followed by ACC formation (via ACC synthase) and subsequent oxidation to ET (via ACC oxidase). Isoprenoids‐derived hormones, including gibberellin (GA) and CK, are synthesized either through the mevalonate pathway (initiated by acetyl‐CoA) or the MEP pathway (using pyruvate and G‐3‐P as substrates). Abscisic acid (ABA) are β‐carotene‐derived hormones biosynthesized through the MEP pathway (Yu et al., 2015). G‐3‐P, glyceraldehyde 3‐phosphate; IPP, isopentenyl pyrophosphate; PEP, phosphoenolpyruvate.

Ethylene–auxin module and sugars crosstalk

The reciprocal interaction between ET and IAA constitutes a central regulatory module in hypoxia responses, with sugar signaling modulating ET‐mediated control of IAA biosynthesis and transport (Nghi et al., 2021; Sasidharan, 2022; Kircher and Schopfer, 2023). Specifically, ET promotes IAA precursor biosynthesis by inducing root‐specific transcription of anthranilate synthase genes weak ethylene‐insensitive 2 (WEI2) and WEI7 (Liu et al., 2022a). However, the regulation of WEI2 and WEI7 alone cannot fully explain hypoxia‐induced IAA accumulation, suggesting that ET coordinates additional IAA biosynthetic pathways to modulate root growth under hypoxic conditions (Stepanova et al., 2005; Eysholdt‐Derzsó et al., 2024). For example, ET accumulation upregulates IAA biosynthetic genes (ASA1, TAA1, TAR2, and YUC3/8) in Arabidopsis roots while suppressing YUC5/6 in seedlings (Eysholdt‐Derzsó et al., 2024). Further, the ET precursor ACC upregulates YUC3, while downregulating tryptophan aminotransferase‐related (TAR) and conjugation and oxidation genes (gretchen hagen 3.6; GH3.6, and dioxygenase for auxin oxidation; DAOs) (Veloccia et al., 2016; Shukla et al., 2019). During root development, polar IAA transport is maintained by pin‐formed (PIN1/4/7) and auxin‐resistant 1 (Aux1), whose expression is upregulated by ACC enzyme by the ethylene response 1 (ETR1) and ethylene‐insensitive 2 (EIN2) signaling cascade (Eysholdt‐Derzsó et al., 2024; Hao et al., 2026). Indeed, ET and IAA independently regulate PIN3 and PIN7, which then directly activate Aux1 and indirectly enhance the PIN protein family, thereby optimizing the IAA distribution for adaptive root growth and bending under hypoxia (Vandenbussche et al., 2012; Eysholdt‐Derzsó and Sauter, 2017; Jiang et al., 2024). ACC modulates IAA distribution by directly influencing the activity of ER‐localized PIN‐LIKES (PILS) transporters and regulating PIN polarity via AGCVIII kinase activation (Miao et al., 2018). In parallel, ET enhances IAA signaling through EIN3‐driven Aux/IAA transcription, influencing processes such as apical hook formation via EIN3–ARF2 interaction and promoting submerged elongation through an ERF72–ARF6 module (Liu et al., 2018; Shin et al., 2022). Collectively, these findings demonstrate that ET orchestrates IAA biosynthesis, transport, and signaling to dynamically reprogram root architecture and adaptive growth under hypoxic conditions.

In addition, ET coordinates hypoxia tolerance by dual regulation of carbohydrate dynamics and anaerobic fermentation through ERFVII proteins, a conserved adaptive strategy that maintains energy homeostasis across plant species (Hsiao et al., 2024; Dalle Carbonare et al., 2025). In Petunia hybrida, ET‐induced PhERF2 enhances hypoxia tolerance by activating sugar transport and alcoholic fermentation (Yin et al., 2019). Similarly, transgenic Nicotiana tabacum overexpressing AdRAP2.3 and AcERF74/75 shows boosted ADH and PDC expression, conferring increased waterlogging resilience in Actinidia deliciosa and A. chinensis, respectively (Liu et al., 2022b). Further, the MEDIATOR SUBUNIT 25 (MED25)–ERFVII module is conserved in Arabidopsis and O. sativa, indicating an evolutionarily conserved role of MED25 in ERFVII‐mediated hypoxia responses (Schippers et al., 2024). For instance, in Arabidopsis, ET treatment upregulates ORESARA1 (ORE1), facilitating nutrient redistribution during submergence, and concurrently, SnRK1 integrates sugar availability with ET signaling to balance energy production and consumption under hypoxia (Wurzinger et al., 2018; Rankenberg et al., 2024). This metabolic interplay establishes an energy‐efficient framework in which ET drives developmental adaptation, while mobilized sugars fuel these processes through glycolysis and fermentation.

Sugars like sucrose and glucose regulate IAA biosynthesis, transport, and signaling, coordinating sink cell expansion and elongation via the acid growth mechanism (Mishra et al., 2022). Specifically, activated auxin‐binding protein 1 (ABP1) stimulates plasma membrane H⁺‐ATPase, acidifying the apoplast to activate cell wall‐loosening enzymes including expansins and xyloglucan endotransglucosylase/hydrolases (Sheen, 2024). Concurrently, IAA is known to activate plasma membrane H⁺‐ATPase pumps (Xu et al., 2025a), while sugars provide the necessary energy to support their activity (Kinoshita et al., 2023; Zeng et al., 2024). Together, this results in membrane hyperpolarization, facilitating H⁺ secretion, K⁺ uptake, and water influx, which are essential for cell division and expansion during hypocotyl elongation, root plasticity, and seed germination (Li et al., 2022; Wang et al., 2024). Further, IAA exerts regulatory control over sugar metabolism by controlling sucrose and starch catabolism, whereas elevated glucose upregulates YUCCA and TAA1 genes to enhance the IAA pathway (Daniel and Hartman, 2024). In shoot meristem activation, HXK‐mediated glucose sensing integrates with IAA signaling to regulate growth. Under energy sufficiency, TOR promotes cell proliferation, whereas SnRK1 antagonizes TOR during energy deprivation (Li and Zhao, 2024). IAA–TOR crosstalk further enhances meristem activity, linking hormonal and metabolic cues, while PIFs integrate sugar and hormone signals to regulate transcriptional programs controlling developmental transitions (Mishra et al., 2022).

Sugars provide metabolic energy, while IAA regulates adaptive responses and modulates sugar partitioning via transporter expression, highlighting a key link between hormonal signaling and metabolic adaptation (Barbier et al., 2015; Qi et al., 2020). Empirical evidence indicates sugar–IAA interplay across species. For example, exogenous sugars promote IAA‐driven O. sativa endosperm development (Yu et al., 2024) and Cucumis sativus root development via the mechanism involving sugar‐mediated YUCCA expression to modulate IAA biosynthesis (Qi et al., 2020). Similarly, sucrose enhances IAA production via PIF‐dependent pathways in Arabidopsis (Kircher and Schopfer, 2023). In addition, adventitious root formation in Malus (Jing et al., 2022), Arabidopsis (Kircher and Schopfer, 2023; Stitz et al., 2023), and Z. mays (Yan et al., 2024) involves stage‐specific coordination between IAA and sugar signaling. Early stages are marked by upregulation of YUC3 and PIN1/2, followed by later activation of SUS1 and SUC5. Collectively, sugar–IAA crosstalk coordinates energy, metabolic, and developmental networks that underpin hypoxia adaptation, providing a mechanistic foundation for improving stress resilience and productivity in future climate‐resilient crops (Figure 2).

Figure 2.

Coordinated regulation of hypoxia responses by sucrose (with other primary sugars), ethylene, and auxin signaling networks

Under energy‐deficient conditions, HRG transcription and translation are suppressed. Conversely, sufficient energy activates TOR‐mediated phosphorylation of ERFVII factors (RAP2.2/2.12), upregulating HRGs (ADH, LDH, and PDC) expression to maintain energy homeostasis. Plants dynamically balance energy demands through autophagy‐driven nutrient recycling and senescence, processes modulated by ET, which induces ATG genes under starvation while being inhibited by high glucose by HXK‐dependent EIN3 destabilization (Hartman et al., 2021). Rapid ET accumulation triggers morphological adaptations, including aerenchyma formation (via PCD), adventitious root growth, shoot elongation, and leaf upright positioning (Takahashi et al., 2018). Concurrently, light‐activated sucrose synthesis in aerial tissues is transported to roots, where it promotes TAA1/YUC‐dependent auxin biosynthesis (IPA‐IAA) to stimulate lateral root initiation (Hajibehzad et al., 2023; Kircher and Schopfer, 2023). ET and hypoxia antagonistically regulate this process by disrupting IAA transport/signaling and stabilizing ERFVII factors (Daniel and Hartman, 2024). ACC, 1‐amino‐cyclopropane‐1‐carboxylic acid; ACO, 1‐aminocyclopropane‐1‐carboxylic acid oxidase; ADH, alcohol dehydrogenase; ARFs, auxin response factors; ATP, adenosine triphosphate; Aux/IAA, auxin/indole‐3‐acetic acid; bZIP, basic leucine zipper; EIN2/3, ethylene‐insensitive2/3; ERFs, ethylene response factors; LBDs, lateral organ boundaries domain; LDH, lactate dehydrogenase; PCD, programmed cell death; PCO, plant cysteine oxidases; PDC, pyruvate decarboxylase; PIFs, phytochrome‐interacting factors; PINs, pin‐formed proteins; SnRK1, sucrose non‐fermenting 1‐related protein kinase 1; TAA/YUC, tryptophan aminotransferase of Arabidopsis; TCA, tricarboxylic acid cycle; TIR1, transport inhibitor response 1; TOR, target of rapamycin.

Cytokinins signaling and sugars crosstalk

CKs and sugars regulate plant growth and stress responses, but their crosstalk under hypoxia remains poorly understood and is further complicated by organ‐specific variation in CK metabolism (Salam et al., 2021). Regarding this, sucrose and palatinose enhance CK biosynthesis in Rosa hybrida by inducing isopentenyltransferases (RhIPT3 and RhIPT5), while in Arabidopsis, glucose upregulates IPT3 and suppresses cytokinin oxidase (CKX4) to promote hypocotyl elongation (Kushwah and Laxmi, 2014; Barbier et al., 2015). Similarly, sugars and CKs coordinately regulate bud outgrowth and shoot branching through reciprocal control of CK biosynthesis, signaling, and sugar partitioning, thereby optimizing resource allocation for axillary bud initiation and growth (Salam et al., 2021; Zafar and Kumar, 2025; Jiang et al., 2025b). This regulation highlights the interplay between CK and sugars, ensuring that resource allocation aligns with the plant's growth priorities (Figure 3).

Figure 3.

Proposed regulatory interplay of sugars, cytokinins, and abscisic acid in hypoxia‐responsive plant growth and development

(A) Under hypoxia, sugar‐CK centers on Tre6P dynamics, where TPS1‐mediated biosynthesis and TPP‐driven degradation fine‐tune Tre6P levels. CK signaling initiates via AHK receptor activation, promoting AHP‐dependent nuclear translocation of ARRs to regulate developmental processes (bud outgrowth, shoot regeneration, and root secondary growth by LBDs) (Ye et al., 2021; Koo et al., 2024). Concurrently, sugar–abscisic acid (ABA) interactions involve Tre6P‐mediated inhibition of SnRK1, which in turn modulates ABA signaling through PYL/PYR receptors to control seed maturation, germination, and stomatal closure (Radchuk et al., 2006; Liu et al., 2024; Ateeq et al., 2025). SnRK1 further amplifies ABA responses by activating downstream factors (FUS3, ABI3, ABI5, and bZIPs) for germination suppression, while PP2C proteins counterbalance this pathway by SnRK1. (B) Hypoxia‐regulated interplay between carbohydrate metabolism, brassinosteroid (BR), and GA signaling during seed germination and coleoptile elongation. Under submergence, hypoxia upregulates BRD1 expression to enhance BR synthesis. This process destabilizes GSK2 kinase through BRI1/BSK2‐mediated phosphorylation, amplifying BR responses (seed germination) and coordinating BR‐dependent/independent mechanisms to maximize coleoptile elongation for hypoxia escape (Hong et al., 2012; Sun et al., 2024). Concurrently, sugar starvation activates Ca²⁺–CBL–CIPK5 signaling to phosphorylate SnRK1A, which stabilizes transcription factor MYBS1, thereby inducing α‐amylase (Ramy3D/Ramy1A) activity for starch degradation in seeds. During dormancy, embryonic GA biosynthesis synergistically enhances α‐amylase production by activating MYBS1 (Veen et al., 2025). ABA2, abscisic acid 2; ABI3/5, abscisic acid‐insensitive 3/5; AHKs, Arabidopsis histidine kinases; AHPAs, Arabidopsis histidine phosphotransfer protein; ARRs, Arabidopsis response regulators; BRI1, brassinosteroid‐insensitive 1; BSK2, BR signaling kinase 2; BZR1, brassinazole‐resistant1; CBL, calcineurin B‐like protein; CIPK15, CBL‐interacting protein kinase 15; CKXs, cytokinin dehydrogenases; CYP735A, cytochrome P450 735A; FUC3, FUSCA 3; GIN1/2, gibberellin‐insensitive1/2; HXK, hexokinase; IPT, isopentenyltransferase; LOG, lonely guy; MYBS1, MYB sugar‐insensitive 1; PLY/PYR, pyr1‐like/pyrabactin resistance; PP2C, protein phosphatase 2C. BRD1, brassinosteroid‐related deficient 1; Ramy1A, rice alpha‐amylase 1A; Ramy3D, rice alpha‐amylase 3D; TPS, trehalose 6‐phosphate synthase.

Recent studies showed that hypoxic stress reduces leaf trans‐zeatin and dihydrozeatin levels, with partial recovery observed upon stress relief (Eerdekens et al., 2024; Geldhof et al., 2024). Waterlogging reduces trans‐zeatin and isopentenyl adenine levels in T. aestivum shoots, likely due to decreased root CK biosynthesis and/or impaired root‐to‐shoot transport (Nguyen et al., 2018). Reduced transpiration under flooding likely decreases CK translocation via xylem, as reported in Zinnia elegans (Demura and Fukuda, 2007) and Phaseolus vulgaris (Lakitan et al., 1992). However, the specific CK biosynthetic enzymes and transporters regulating reduced xylem loading under hypoxia remain unknown, and CK responses to flooding and waterlogging are species‐specific (Tamang et al., 2021). Similarly, in S. lycopersicum, hypoxia upregulates CKX2 while downregulating CYP735A1/A2 (reducing trans‐zeatin formation in roots) (De Ollas et al., 2021). Conversely, a study in T. aestivum show upregulated CK biosynthetic genes like IPT and LONELY GUY (LOG) during prolonged hypoxia (Nguyen et al., 2018). Given the central roles of CKs in growth regulation and sugars in energy signaling, dissecting their crosstalk through genetic approaches, particularly using CK‐ and sugar‐signaling mutants, represents an important future research direction for understanding plant adaptation to hypoxic stress.

Crosstalk between ABA signaling and sugars

The interaction between ABA signaling and sugar metabolism constitutes a key regulatory module linking energy status with growth and stress adaptation. In this network, Tre6P serves as a mediator of ABA–sugar crosstalk through SnRK1 inhibition and activation of ABI3/ABI5‐dependent signaling pathways (Li and Zhao, 2024). More broadly, SnRK1 acts as a central integrator of metabolic and hormonal signals, modulating ABA responses in a species‐specific manner (Tian et al., 2020; Renziehausen et al., 2025). In Pisum sativum, SnRK1 knockdown reduces ABA accumulation and ABI3 expression, whereas in Arabidopsis, SnRK1 enhances ABA biosynthesis via FUS3 activation; together, these findings position FUS3 downstream of SnRK1 and highlight its conserved role in regulating ABA‐mediated germination (Radchuk et al., 2006). Furthermore, SnRK1 regulates ABA signaling by phosphorylating ABI5 and bZIP12, core modulators of seed maturation and seedling growth (Carianopol et al., 2020). In contrast, ABI1 and protein phosphatase 2 C A (PP2CA) restrain SnRK1 activity, assembling a negative feedback loop (Leene et al., 2022). Recent reports in Avicennia marina indicate that tidal submergence enhances Tre6P accumulation while reducing trehalose levels, emphasizing the central role of primary sugars in hypoxia acclimation. Tre6P could impact ROS homeostasis and regulate ABA signaling (Song et al., 2025). Indeed, Tre6P accumulation may signal broader submergence adaptation, though its role remains unresolved. Overall, trehalose metabolism, ABA signaling, and SnRK1 act in concert, with PP2C phosphatases and bZIP proteins as key regulators of energy sensing (Figure 3A; Paul et al., 2008; Wang et al., 2025a).

Sugar‐induced ABA synthesis triggers PP2C, which impairs SnRK2, thereby activating ABRE‐binding transcription factors that, in turn, promote Tre6P‐mediated regulation (Carianopol et al., 2020). Concurrently, alterations in sugar and ABA levels stimulate the expression of ANAC060, which attenuates sugar‐mediated gene expression and ABA signaling (Kunkowska et al., 2023). This biphasic modulation fine‐tunes photosynthesis, with ABA promoting plant resilience against post‐submergence recovery (Wu et al., 2019; Kunkowska et al., 2023). Several studies show that hypoxia markedly reduces ABA levels across species, including deepwater O. sativa (Ashikari et al., 2025), Nasturtium officinale (Müller et al., 2021), and S. lycopersicum (De Ollas et al., 2021). This decline is generally associated with suppressed ABA biosynthesis and enhanced catabolism, although species‐specific variations in catabolic regulation have been reported in T. aestivum (Nguyen et al., 2018) and S. dulcamara (Dawood et al., 2016), contributing to shoot elongation under submergence (Eerdekens et al., 2025). Notably, submergence 1 A (SUB1A) enhances ABA sensitivity in O. sativa, improving drought, soil compactness resilience, and post‐submergence recovery (Alpuerto et al., 2022; Zafar and Canto‐Pastor, 2025). Collectively, these findings identify ABA as a negative regulator of shoot elongation and adventitious rooting under hypoxia, driven by reduced biosynthesis and enhanced catabolism.

Further, the interaction between sugar and ABA signaling pathways plays a central role in regulating plant growth and hypoxia adaptation (Figure 3). A key mechanism in this process involves reciprocal regulation between ABA and TOR through SnRK2‐mediated signaling (Shi et al., 2018). Under normal conditions, TOR kinase phosphorylates ABA receptor pyrabactin resistance‐like (PYL), thereby inhibiting stress responses by disrupting PYL–ABA and PYL–PP2C interactions, and maintaining SnRK2 in an inactive state. However, ABA‐activated SnRK2s phosphorylate regulatory‐associated protein of TOR (RAPTOR), leading to TOR complex dissociation under stress (Belda‐Palazón et al., 2020). Consequently, TOR suppresses ABA signaling under normal conditions and ABA inhibits TOR during stress, ensuring a balance between growth and stress adaptation in reciprocal way (Wang et al., 2018). During hypoxia, this regulatory balance is initiated by early oxygen‐sensing mechanisms. Hypoxia triggers rapid upstream signaling events, including membrane depolarization, cytosolic Ca²⁺ transients, and ROS bursts, followed by stabilization of ERFVII transcription factors, which collectively feed into downstream ABA–TOR–sugar regulatory networks to coordinate growth and stress responses (Schmidt et al., 2018; Hartman et al., 2021; Liu et al., 2022a; Fan et al., 2023).

The molecular interplay between sugar and ABA signaling has been extensively studied through glucose‐insensitive mutants, including gins, abi4, abi5, abas, and ctr1, which influence ABA biosynthesis during stress (Arroyo et al., 2003). For example, glucose enhances ABI4 and ABI5 expression while reducing constitutive triple response 1 (CTR1), demonstrating an antagonistic interaction in the regulation of ABA‐responsive genes (Ayub et al., 2025). During early seedling development, glucose signaling modulator 1 (GSM1) negatively regulates ABI4‐mediated glucose and ABA signaling. Consequently, the mutants lacking GSM1 show heightened sensitivity to ABA under high‐glucose conditions, reinforcing the established role of ABI4 as a central convergence point for glucose and ABA signaling pathways (Zheng et al., 2019). In contrast, SCARECROW transcription factors suppress ABI4 expression in the root apical meristem, reinforcing its central role in the ABA–sugar regulatory network (Hernández‐Bernal et al., 2021). Molecular analyses support this network‐level integration, showing strong co‐expression of sugar transporters, metabolic enzymes, and ABA‐related genes in guard cells. This highlights ABA's role in coordinating sucrose transport and metabolism to optimize stomatal function across species, including Arabidopsis (Flütsch and Santelia, 2021; Asim et al., 2023), S. lycopersicum, and M. domestica (Zhu et al., 2023). Regarding hypoxia and subsequent reoxygenation, ABA also plays a central role in stomatal regulation (Iida et al., 2016; León et al., 2021). This process is further regulated by sugar signaling, as sucrose functions both as an osmotic driver and as a signaling molecule in guard cells (Flütsch and Santelia, 2021). Through this interaction, sugar availability can modulate ABA‐dependent ion fluxes and turgor adjustments, and thereby influence stomatal aperture and optimize gas exchange and water use efficiency. This coordinated ABA–sugar regulatory network enables rapid stomatal responses during oxygen fluctuations, linking cellular energy status with whole‐plant physiological adaptation. Taken together, reciprocal regulation between ABA and sugar pathways fine‐tunes growth–stress trade‐offs.

Gibberellin–ethylene and brassinosteroid coupling with carbohydrates

In deepwater rice, ET promotes growth via GA‐driven elongation and energy starvation signaling, coordinated by AtERF11 through ET repression and GA/BR activation (Sun et al., 2024). In addition, increased ET levels stabilize OsEIL1, a transcription factor of GA biosynthetic genes (GA20ox1/2/3/5), driving GAs accumulation and cell expansion during primary root development and elongation in O. sativa seedlings (Qin et al., 2022). Hypoxia‐responsive gene expression supports this process, with the accelerator of internode elongation 1 promoting meristem cell division and downregulation of the decelerator of internode elongation 1 facilitating GA‐driven internode elongation (Nagai et al., 2020). Collectively, these findings indicate that deepwater rice uses a hormonally integrated strategy in which ET promotes growth via GA while optimizing energy allocation under hypoxia. This balance between growth and metabolic constraint reflects a coordinated survival mechanism linking developmental plasticity with environmental sensing.

Although GA are well‐characterized growth regulators, their interaction with sugar metabolism under hypoxia remains unclear, with reciprocal regulation between GA signaling and sugar availability (Robil et al., 2025). Early genetic evidence from sugar‐insensitive1 (sis1) and Glc‐insensitive4 (gin4) mutants reveals functional convergence, with dual resistance to sugar and GA signaling during seed germination (Veen et al., 2025). In O. sativa, starch mobilization during germination is mediated by distinct α‐amylase isoforms with oxygen‐dependent regulation (Lasanthi‐Kudahettige et al., 2007). Regarding this, RAmy3D is strongly induced under hypoxic or anoxic conditions, and drives starch degradation during anaerobic germination, whereas RAmy1A is predominantly activated during aerobic germination in a GA‐dependent manner (Loreti et al., 2003). Notably, hypoxia‐induced RAmy3D expression is synergistically modulated by GA (Kaneko et al., 2002), BRs, and sugar starvation signals, thereby ensuring sufficient fermentable sugars and ATP production to sustain coleoptile elongation under low‐oxygen conditions (Xiong et al., 2021; Lima et al., 2024). Further, the CIPK12–SnRK1A–MYBS1 cascade links oxygen deficiency signals to sugar starvation response, coordinating energy production with submergence adaptation in cereal crops (Fan et al., 2023).

O. sativa shows superior germination and coleoptile elongation under hypoxia, attributed to enhanced oxidative phosphorylation in carbohydrate metabolism and elevated GA activity (Magneschi et al., 2009; Zhang et al., 2021). Under submergence, GA accumulation activates the transcription factor SUB1A, which restrains GA‐mediated growth by promoting the accumulation of GA signaling repressors (slender rice 1; SLR1 and SLRL1), thereby suppressing GA‐inducible gene expression and limiting carbohydrate catabolism (Bailey‐Serres et al., 2010). Notably, during prolonged submergence, SLR1 levels decline in Sub1A‐overexpressing lines, while the DELLA‐lacking repressor SLRL1 accumulates, ensuring sustained growth repression under low‐oxygen conditions (Fukao and Bailey‐Serres, 2008). Counteractively, SnRK1/2 kinases and DELLAs promote GA biosynthesis to enhance metabolic activity (Robil et al., 2025). This regulatory divergence drives two distinct survival strategies: An escape strategy of rapid growth to outpace rising water and a quiescence strategy of suspended growth to conserve energy for recovery (Pucciariello and Perata, 2024). Beyond O. sativa systems, GA and ET coordinately regulate sugar‐mediated growth responses across plant species, including shoot elongation in Callitriche and O. sativa, petiole extension in Rumex palustris, hyponastic growth in N. tabacum, and apical hook formation in Arabidopsis (Nagai et al., 2020).

Besides GA, recent studies indicate that BR modulates seed germination and coleoptile elongation in plants (Figure 3B). For example, hypoxia induces the expression of brassinosteroid‐deficient dwarf 1 (BRD1) to promote BR biosynthesis and destabilizes glycogen synthase kinase 2 (GSK2), a negative regulator of signaling, thereby modulating redox balance and hormonal crosstalk (Xiong et al., 2022). Additionally, BR signaling promotes seed germination by brassinazole‐resistant 1 (BZR1), which directly activates RAmy3D expression to promote α‐amylase‐mediated starch degradation. This BZR1–RAmy3D module operates parallel to, yet independently of, the GAMYB–RAmy1A pathway, contributing to sugar mobilization during submergence (Sun et al., 2024). In contrast, other cereals like Z. mays, T. aestivum, and Hordeum vulgare fail to accumulate α‐amylase under hypoxia, leading to stalled starch hydrolysis and germination failure (Rolletschek et al., 2025). Thus, α‐amylase regulation across species serves as a useful model for energy starvation signaling and GA–hormone interactions under hypoxia. However, the molecular integration of GA, ET, BR, and sugar signaling in stress‐adaptive growth remains unclear and requires further investigation, particularly across contrasting flood‐response species.

Collectively, the above‐mentioned findings and crosstalks highlight the pivotal role of sugar signaling and energy‐sensing networks in coordinating plant growth, development, and stress adaptation through extensive interactions with phytohormonal pathways. The sucrose‐derived signal Tre6P acts as a key indicator of cellular carbon status by inhibiting SnRK1 activity, while TOR kinase antagonizes SnRK1 to promote growth under energy‐sufficient conditions, thereby linking energy availability to developmental and stress‐responsive processes (Xiong et al., 2013; Wurzinger et al., 2018; Wu et al., 2019). Beyond its role in energy sensing, Tre6P functions as a central regulatory hub that integrates metabolism with development by modulating ABA signaling, coordinating sugar utilization with CK, and promoting seed filling through IAA biosynthesis (Fàbregas et al., 2026; Zhao et al., 2025; Xu et al., 2025b). Furthermore, plant development and environmental adaptation are governed by complex sugar–hormone metabolic crosstalk, whereby GA activity is coupled to sugar availability to sustain growth, ABA integrates metabolic and calcium signals during germination, and ET and BRs reprogram carbon allocation and utilization under stress conditions (León and Sheen, 2003; Gibson, 2004). Together, these interconnected signaling networks enable plants to integrate metabolic status with hormonal and environmental cues, thereby optimizing growth, development, and stress resilience.

SYNTHETIC INTEGRATION: COUPLING OXYGEN SENSING WITH SUGAR–HORMONE CIRCUITS FOR HYPOXIA RESILIENCE

Recent advances have equipped researchers with a sophisticated suite of tools to detect, image, and manipulate oxygen levels in both plants and animals (Van Dongen and Licausi, 2015; Schmidt et al., 2018; Iacopino et al., 2019; Wagner et al., 2019; Weits et al., 2021; Panicucci et al., 2025). These range from physical sensors (e.g., micro‐electrodes and Clark‐type electrodes) to advanced molecular probes (Rijnders et al., 2000), including microfluidic O₂ sensor systems (equipped with phosphorescence) (Brennan et al., 2014), fluorescent protein‐based reporters (via Förster resonance energy transfer; FRET) (Erapaneedi et al., 2016; Perri et al., 2025), imaging platforms such as fluorine‐19 nuclear magnetic resonance (¹⁹F NMR) (Yu et al., 2005), magnetic resonance imaging (MRI), and positron emission tomography (PET) (Piovesan et al., 2021; Perez et al., 2023). These tools enable mapping of hypoxic niches. For example, reconstitution of the Arabidopsis PCO–ERFVII module in yeast shows that it is sufficient for rapid, quantitative hypoxic responses with conserved dynamics (Lavilla‐Puerta et al., 2026). In addition to ERFVIIs, recent studies have revealed that the Polycomb Repressive Complex 2 (PRC2) subunit VERNALIZATION2 (VRN2) also functions as an oxygen‐sensitive component of the N‐degron pathway, acting both as an oxygen sensor and as a chromatin regulator to establish adaptive flooding stress memory in plants (Kosmacz et al., 2015; Gibbs and Holdsworth, 2020; Akter et al., 2026; Maric et al., 2026). Synthetic oxygen sensors are thus enabling engineered circuits that program metabolic responses to low oxygen.

The advent of synthetic biology has enabled a new generation of metabolic engineering in plants, with advances in core pathways demonstrating remarkable potential for enhancing crop yield and stress tolerance (Anderson et al., 2023; Zhang et al., 2025; Ateeq et al., 2026). A primary strategy to enhance hypoxia resilience involves optimizing the Calvin–Benson–Bassham (CBB) cycle and carbohydrate transport systems to sustain carbon and energy availability during oxygen deprivation. Engineered improvements in key CBB enzymes, including RuBisCO and sedoheptulose‐1,7‐bisphosphatase, enhance photosynthetic efficiency and carbon fixation (Flecken et al., 2020; Stitt et al., 2021; Raines, 2022; Qin et al., 2025), while targeted manipulation of sugar transporters improves source–sink balance and carbohydrate allocation (Abelenda et al., 2019; Singh et al., 2023). Together, these metabolic engineering approaches increase sucrose availability and mobilization, thereby supporting glycolysis, fermentative metabolism, and cellular energy homeostasis under hypoxic conditions. Extending this, synthetic biology has enabled pathway rewiring, such as introducing a bacterial route into chloroplasts to bypass photorespiration by converting glycolate directly into glycerate (Kebeish et al., 2007; South et al., 2019). This strategy boosts photosynthesis and sugar production, demonstrating carbon flux reprogramming, with Tre6P functioning as a central growth‐regulating carbon signal (Figueroa and Lunn, 2016; Fichtner and Lunn, 2021; Eh et al., 2024). This role is exemplified in O. sativa, where OsTPP7 fine‐tunes Tre6P levels to regulate carbon allocation. Under low‐sugar conditions of anaerobic germination (Kretzschmar et al., 2015), OsTPP7 promotes Tre6P turnover, enhancing sink strength and mobilizing sucrose and starch to fuel rapid coleoptile elongation (Lunn et al., 2014; Yadav et al., 2014)—a key trait for low‐oxygen tolerance. This mechanism underscores Tre6P's role as a central energy sensor and integrator, directly modulating the master growth (via TOR) and stress/energy‐sensing (via SnRK1) kinase pathways (Zhang et al., 2009; Figueroa and Lunn, 2016; Griffiths et al., 2016a; Baena‐González and Hanson, 2017), while also modulating hormonal signaling networks (Fàbregas and Fernie, 2021; Asim et al., 2023; Fàbregas et al., 2026).

Spatiotemporal control of hormone dynamics is essential for stress adaptation. Engineered circuits, such as synthetic hormone‐responsive PYR1 receptors, enable on‐demand stress tolerance independent of native signaling (Park et al., 2015). Similarly, advanced genetically encoded biosensors now enable real‐time visualization of hormone dynamics. Sensors like ABAleons and ABACUS1 quantify ABA at a single‐cell resolution (Jones et al., 2014; Rowe et al., 2023), while the nlsGPS1 FRET biosensor allows live tracking of nuclear GA levels (Rizza et al., 2019). Concerning CK, mapping receptor trafficking has provided a blueprint for synthetically rewiring signaling (Kubiasová et al., 2020). More recently, the synthesis of Sensl, the first ratiometric sensor for SL signaling, allows noninvasive monitoring in intact plants (Li et al., 2025). This toolkit enables hypoxia‐responsive hormone circuits by coupling stress‐activated expression with biosensor feedback to create closed‐loop systems that dynamically balance growth and survival.

Due to space constraints, some important and active areas of sugar and hormone research cannot be covered in depth; the reader is referred to previous reviews that cover these areas (Gibson, 2004; Fernandez et al., 2010; Eveland and Jackson, 2012; Dominguez et al., 2013; Eom et al., 2015; Griffiths et al., 2016b; South et al., 2018; Margalha et al., 2019; Morales‐Herrera et al., 2024; Wittmer et al., 2025; Yu and Jiang, 2026). The discussion here has highlighted the advantages and limitations of current approaches in oxygen sensing, sugar, and hormone circuits engineering (Patrick et al., 2013; Leydon et al., 2020; Huang et al., 2021; Licausi and Giuntoli, 2021; Weits, 2021; Shukla et al., 2026; Bailey‐Serres et al., 2025). Thanks to these tools, we can address a key question: How to integrate synthetic oxygen sensors with engineered sugar–hormone biosensors and transporters to build closed‐loop regulatory circuits? Such systems could enable SMART crops that autonomously detect hypoxia, integrate stress signals via sugar–hormone networks, and activate adaptive responses to maintain survival and yield stability (Figure 4). Despite the promise of SMART crops, several challenges remain. Extensive rewiring of interconnected sugar–hormone–oxygen networks may lead to unintended pleiotropic effects. In addition, limited transformation efficiency in non‐model crops, particularly woody fruit crops, remains a major bottleneck, making stable genetic transformation, mutant development, and functional validation of genes highly challenging. These difficulties are further compounded by complex and less characterized metabolic reprogramming in such species, which can affect transgene stability, phenotype reproducibility, and downstream trait expression. Addressing these constraints will be essential for the practical translation of this framework into crop improvement. This represents the ultimate translation of the “sugar–hormone duet” from an observed dialogue into a designed, integrated system for hypoxia resilience.

Figure 4.

From natural adaptation to synthetic circuits: An engineering roadmap for hypoxia‑resilient SMART crops

(A) Under hypoxia, conserved energy and oxygen sensors perceive stress (Wang et al., 2017), triggering crosstalk between sugar metabolism and hormonal signaling to coordinate adaptive responses. (B) A synthetic‑biology approach proposes engineering SMART crops by integrating synthetic oxygen sensors, actuator modules (carbon fixation, hormonal control, and transport systems), and biosensor‑driven feedback/feedforward into coherent circuits. This enables autonomous resilience by optimizing energy homeostasis and hormonal levels under hypoxic stress, ultimately enhancing plant growth, stress adaptation, productivity, and yield stability under waterlogging conditions.

CONCLUSION AND FUTURE PERSPECTIVES

Plant survival under hypoxia depends on the coordinated interplay between sugar metabolism and phytohormone signaling. Sugars function not only as energy sources but also as signaling molecules that regulate metabolic reprogramming through central hubs such as TOR, SnRK1, and Tre6P. Simultaneously, phytohormones including ET, IAA, ABA, CK, GA, and SL orchestrate developmental and physiological adaptations that enable hypoxia acclimation. Together, sugar signaling and phytohormonal networks constitute an integrated regulatory framework that coordinates metabolic adaptation, growth regulation, and stress resilience under hypoxic conditions. Despite significant advances, translating this knowledge into climate‐resilient crops remains a major challenge. Future efforts should move beyond descriptive studies toward engineering integrated regulatory systems that combine oxygen sensing, sugar signaling, and hormonal control with spatial and temporal precision. The development of synthetic and feedback‐regulated circuits, coupled with tissue‐specific and hypoxia‐inducible expression strategies, offers promising opportunities to minimize fitness penalties while enhancing adaptive responses. Ultimately, integrating metabolic regulation with programmable hormonal networks may pave the way for developing SMART crops with improved flooding resilience and stable productivity under changing climatic conditions.

GENERATIVE AI USAGE STATMENT

During the preparation of this work, the authors used DeepSeek and Gemini AI for text polishing and language refinement. The authors reviewed and edited all AI‐generated content as necessary and take full responsibility for the final published work.

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

AUTHOR CONTRIBUTIONS

M.A. (Muhammad Ateeq) and J.L., conceptualized the study and wrote the manuscript. M.A. (Muhammad Asim), X.H., M.A.A., and K.Z. curated the literature and prepared figures. S.S. and J.L. revised the manuscript. All authors have read and approved of the contents of this article.

Biographies

Ateeq, M. , Ashraf, M.A. , Asim, M. , Huang, X. , Zhu, K. , Shabala, S. , and Liu, J. (2026). Duet between sugars and hormones: The molecular dialogue fine‐tuning hypoxia acclimation in plants. J. Integr. Plant Biol. 68: 3086–3106.