Table 1.
Summary of the main physiological and molecular phenomena awaken by specific stress factors in Y. lipolytica cells
Stress factor | Cellular response | References |
---|---|---|
Low-oxygen availability | ||
Different pO2 levels | Glucose concentration-dependent filamentation mediated via RAS-cAMP-PKA; in the presence of cAMP – no filamentation | (Ruiz-Herrera and Sentandreu 2002; Bellou et al. 2014; Timoumi et al. 2017a, 2018; Gorczyca et al. 2020; Lesage et al. 2021) |
Downregulation of lipid biosynthesis | ||
Restorable growth rate limitation | ||
Acidity – pH | ||
pH 3.0 | Higher energy requirement | (Madshus 1988; Cogo et al. 2020) |
Increased abundance and activity of plasma membrane H + -ATPase Pma1p | ||
pH 4.0/3.0 | Intracellular proton extrusion across the mitochondrial inner membrane – the major mechanism contributing to the pH homeostasis | (Guo et al. 2016) |
Increased energy demand – upregulation of glycolysis -– Pgk1p, Gut2p, Eno2p, Tpi1p, Tdh3p, Fba1p, Pck1p | ||
Key role of mitochondria (and increased energy demand): Upregulation of mitochondrial proteins – Por1p, Cit1p, Pda1p, Pdb1p, Mdh1p, Icl1p, Kgd2p, Acs2p Upregulation in mitochondrial electron transport chain and ATP synthesis – Nuamp, Nuemp, Nufmp, Qcr2p, Atp1-2–3-7p, Cdc48p, Afg1p | ||
Onset of oxidative stress response: Increased synthesis of amino acids– Aat2p, Leu1p, Gcv2p, Sam2p, Met6p, Ilv5p, Ses1p, Gat1p, Shm1p Upregulation of molecular chaperones (Kar2p, Sse1p, Ssa4p) Upregulation of Sod2p | ||
Enhanced synthesis of aKGA | ||
pH 9.0 | Drop in intracellular sugar amounts by 25% | (Sekova et al. 2019) |
Changes in intracellular sugar composition – increase in MAN, no glucose, no TRE | ||
Drop in storage lipids – lipid bodies and/or membrane lipids by ~ 30% and 36% | ||
Increased level of saturated fatty acids (sFAs) in mitochondria | ||
Upregulation of Sod2p activity | ||
Reduced glutathione (GSH) concentration | ||
pH 9.0 | Increased chaperoning capacity – rotamase, Hsps | (Sekova et al. 2021) |
Substantial changes in mitochondria activity – upregulation of malate dehydrogenase, VDAC porin, NADPH dehydrogenase, mitochondrial chaperones, and pore constituents Mitochondrial VDAC was deemed as one of the key proteins responding to the alkaline pH | ||
Enhanced energy demand – upregulation of TPI1/Tpi1p and GAPDH | ||
pH 4.5/pH 7.0 | Glucose concentration-dependent filamentation mediated via RAS-cAMP-PKA; in the presence of cAMP – no filamentation | (Timoumi et al. 2017b; Lesage et al. 2021) |
Temperature | ||
38 ℃ | twofold increase in the total cytosolic sugar content with concurrent substitution of MAN for TRE; 10 × increased concentration of arabitol | (Sekova et al. 2019) |
Drop in the storage and membrane lipid levels (by 35%), changes in their composition (like > threefold decrease in the sterols content and appearance of some sterol esters) | ||
Increased activities of Sod2p and catalase Ctt1p | ||
threefold increase in GSH level, tenfold increase in glutathione disulfide (GSSG) pool | ||
Lipid bodies-nucleus-mitochondria continua – active migration of lipids | ||
37 ℃ | Enlargement of mitochondria, enhanced number and enlargement of peroxisomes, formation of lipid and polyphosphate granules, formation of globular surface structures, enriched in silicone | (Biryukova et al. 2011; Arinbasarova et al. 2018) |
Dimorphic transition – unipolar growth, asymmetric division, large, polarly located vacuoles, and repression of cell separation after division | ||
37 ℃ | Filamentation – elongation factor increased by 25% | (Kawasse et al. 2003) |
42 ℃ | Increased concentration of MAN (fourfold) and aKGA (threefold) | (Kubiak et al. 2021) |
38 ℃ | Induction of heat-shock proteins synthesis | (Sekova et al. 2021) |
Cell shrinkage – cofilin (F20856p) | ||
Upregulation in thioredoxin (Trx1p), formate dehydrogenase (Fdh1p) | ||
Upregulation of fructose-bisphosphate aldolase (Fba1p) enhanced TRE synthesis | ||
Thermotolerant strain BBE-18 | Upregulation of amino acids synthesis, including Ala, Arg, Asn, Gln, and Met | (Qiu et al. 2021) |
Upregulation of phosphoglucomutase PGM1, pyruvate kinase PYK1, and erythrose reductase ER3 | ||
Key role of thiamine synthesis (E32681g, E35222g, A12573g, and F26521g) evidenced | ||
Dehydration | ||
Drying or freezing | Injury of the plasma membrane, changes in its fluidity and organization, lipids peroxidation, nucleic acids degradation, proteins dehydration and aggregation, cell wall disruption, causing cell shape alteration, and loss of cell integrity | (Pénicaud et al. 2014) |
Oxidative agents | ||
0.5 mM H2O2 | Accumulation of polyphosphate granules | (Biryukova et al. 2011) |
0.5 mM H2O2 | Globular structures on the cell wall surface – surface globules contain silicone | (Arinbasarova et al. 2018) |
Formation of the multi-layered plasma membrane and multiple membrane vesicles localized in proximity to the cell wall | ||
Abrupt increase in cAMP and the following drop – activation of stress defense mechanisms | ||
1 mM paraquat hyperbaric air (3 or 5 bar) 50 mM H2O2 |
Lipid peroxidation | (Lopes et al. 2013) |
Increased GSH content | ||
Upregulation of Glr1p and Sod2p activity | ||
H2O2 – Ctt1p activity induction | ||
20 mM H2O2 | Induced filamentation | (Kawasse et al. 2003) |
Acetate | Decreased lipogenic potential | (Xu et al. 2017) |
Toxic metals and chemicals | ||
Heavy metal ions | Filamentation | (Bankar et al. 2018) |
Formation of nanostructures on the yeast cell surfaces | ||
Faulty cytokinesis | ||
Fe2+ and pH 3.0 | Decreased abundance and activity of plasma membrane H + -ATPase Pma1p | (Cogo et al. 2020) |
50 µM uranium | Increased cell size, irregular cell surfaces, membrane permeabilization | (Kolhe et al. 2020) |
Enhanced ROS generation, lipid peroxidation, transient RNA degradation, and protein oxidation | ||
Upregulation of Sod2p activity, but not Ctt1p | ||
Disappearance of vacuoles and other intracellular organelles | ||
50 µM uranium | Upregulation of transmembrane transporters (MFS and ATPase-coupled transmembrane transporter) | (Kolhe et al. 2021) |
Oxidative stress response – upregulation of GSH transferase/peroxidase, peptide-methionine (R)-S-oxide reductase and other oxidoreductases | ||
DNA damage repair – mismatch repair, chromatin condensation (RCC1) | ||
Structural rearrangements in cell wall – 1,3-β-glucanosyltransferase, chitin synthase | ||
Cell division arrest at G2 phase – SMC2, SMC4, YCS4, YCG1, HOF1 | ||
Ionic liquid | Damage of cell envelope – cavities, dents, and wrinkles | (Walker et al. 2019) |
Onset of restructuring within the cell wall and plasma membrane | ||
Sterol biosynthesis was the only “lipid pathway” significantly perturbed | ||
twofold increase in ergosterol content | ||
Osmo-active compounds | ||
Different effectors |
Induction of HOG pathway: Sln1-Ypd1-Ssk1/2 – cytoplasmic functions of Hog1p: stabilization of stress-response transcripts Ubp3-driven turnover of specific transcription factors and/or RNA Pol II Sln1-Ypd1-Skn7 – nuclear functions of Hog1p: direct interaction with transcription factors and chromatin remodeling factors transcription of stress-response genes |
|
A rapid and transient delay at various stages of the cell cycle | ||
Depending on the osmo-active compound – induction or repression of rs-Prot synthesis | ||
0.5–1.0 M glycerol/glucose | Induction of ERY-dependent but HOG-independent osmoprotection mechanism | (Rzechonek et al. 2020) |
6–9% NaCl | Decrease in cell size – rapid concentration of intracellular solutes, e.g., amino acids like proline, alanine | (Andreishcheva et al. 1999) |
Rapid action of cell membrane pumps and cytoskeleton | ||
3% NaCl = 4.21 Osm kg−1 | Promoted synthesis of ERY – upregulation AKRs: Gcy12p, Tkl1p and Gcy15p | (Yang et al. 2015) |
Increased demand for energy – upregulation of a panel of proteins involved in glycolysis (Tpi1p), TCA (AcnAp; Mdh2p), and respiration (Cox4p, Mcr1p) | ||
Onset of oxidative stress response – upregulation of Ctt1p, Sod2p Ahp1p, Sti1p, Hsp20p, Hsp12p | ||
Upregulation of amino acids synthesis – Met6p, Shmtp | ||
Downregulation of Gdh1p to decrease amino acids efflux to TCA | ||
Adjustment of ions equilibrium – downregulation of membrane K + channel | ||
Downregulation of protein synthesis (Tef1p, ribosomal 60S proteins L2 and L4, seryl-tRNA synthetase) | ||
Upregulation of Prb1p vacuolar protease | ||
360 g L−1 sorbitol = 3 Osm kg−1 | Upregulation of AKRs involved in polyols synthesis – 7 × higher concentration of MAN, 2 × ERY – Gcy13p, Gcy12p, A19910p, F24937p, D08778p | (Kubiak-Szymendera et al. 2021a, b) |
Downregulation of TCA and FA synthesis – threefold reduction in CA concentration | ||
High increase in chaperoning and folding capacity – HSP20, STI1, FMO1, SSA6/7, and Ssa6p, Ssa8p, Hsp104p, Hsp90p, ER-localized E25696p, F00880p, and mitochondrial Hsp78p, Isu1p | ||
No evidence for HOG1 upregulation at gene expression/protein abundance level, but upregulation of SKN7 and SKO1 | ||
Enhanced TRE synthesis – TPS1, TPS2, TPS3 | ||
Onset of oxidative stress response | ||
Enhanced demand for energy – upregulation of D08602p, F24409p, D09933p, and transcriptional activation of TPI1 | ||
Sequestration of membrane channels and transporters – upregulation of cellular membrane invagination and endocytosis factors (Pil1p/Lsp1p), vesicle transportation (B14102p, F27379p), and the major vacuolar protease Prb1p | ||
Downregulation of protein synthesis-related processes – Tef1p, ribosomal 60S proteins L2 and L4, and eight amino acid-tRNA synthetases, ribosome biogenesis (E31625p, F12661p) and biosynthesis of amino acids (Aro10p, Bat2p, Pro3p, CysK-Met25p, MetBp) increased amounts of uncharged tRNAs | ||
Over-synthesis of rs-Prots – strongly dependent on biochemical properties of the rs-Prots | ||
Over-synthesis of burdensome r(s)-Prots | Significant increase in the synthesis of stress-response molecule – MAN | (Korpys-Woźniak et al. 2020) |
Over-synthesis of two demanding rs-Prots | Significantly increased demand for the substrate even at the reduced growth rate | (Gorczyca et al. 2022) |
Over-synthesis of burdensome r(s)-Prots | Upregulated biological process – ion homeostasis | (Korpys-Woźniak and Celińska 2021) |
Increased abundance of vacuolar sorting and vacuolar proteases | ||
Downregulation of ribosome biogenesis and rRNA processing | ||
Over-synthesis of highly synthesized and highly secreted rs-Prots | Increased energy demand – enhanced expression of genes localized to mitochondria | |
Significant upregulation of oxidative stress response genes | ||
Downregulation of protein degradation, autophagy, and vacuolar protein sorting factors | ||
Growth arrest phase (G1 phase) | ||
Released ribosome assembly from inhibition | ||
Over-synthesis of two rs-Prots – larger and smaller | Accumulation of the larger protein’s transcript – indicating insufficient translation capacity | (Swietalski et al. 2020) |
Limitation of the smaller protein secretion level | ||
Over-synthesis of two complex rs-Prots | Accumulation of saturated FAs—marker of ER-stress | (Wei et al. 2019, 2021) |
Competition among synthesis/secretion of the protein and lipid synthesis |