Table 1.

Brief descriptions of the mechanisms linked to the processes underlying acetic acid toxicity, as enumerated in Fig. 1. These descriptions may also refer to mechanisms of response and adaptation to acetic acid, as depicted in Fig. 2, where necessary, for clarity.

Process	Mechanism	References
(1) Acetic acid passive diffusion	Acetic acid in its undissociated form (when extracellular pH < pKa) crosses the PM through passive diffusion, likely adopting a dimeric structure	Casal et al. (1996), Mollapour and Piper (2007), Lindahl et al. (2018), Pem et al. (2023)
(2) Intracellular acidification	Cytosolic dissociation of acetic acid (where pH > pKa) leads to the accumulation of protons and subsequent intracellular acidification	Pampulha and Loureiro-Dias (1989), Arneborg et al. (2000), Antunes et al. (2023)
(3) Reduction in glycolytic flux	Cytosol acidification inhibits the activity of several glycolytic enzymes	Pampulha and Loureiro-Dias (1990), Almeida et al. (2009), Stratford et al. (2013a), Dong et al. (2017)
(4) PM potential dissipation	The accumulation of protons intracellularly leads to the depolarization of plasma membrane through the dissipation of the H+ gradient	Godinho et al. (2018), Antunes et al. (2023)
(5) Decrease in ATP pools	Activation of the ATP-dependent efflux of protons, through the PMH+-ATPase Pma1, and of acetate, via MDR/MXR transporters (Fig. 2), results in a depletion of cellular ATP pools	Pampulha and Loureiro-Dias (2000), Fernandes et al. (2005), Ullah et al. (2013a), Zhang et al. (2022)
(6) Inhibition of nutrient uptake	A reduction in intracellular ATP pools, coupled with disruptions in proton gradients, hinders the ATP-dependent symport of nutrients such as amino acids	Almeida et al. (2009), Ding et al. (2013), Dong et al. (2017)
(7) Oxidative stress	Acetate has been shown to have a prooxidant effect, leading to activation of the antioxidative response (Fig. 2)	Semchyshyn et al. (2011), Guaragnella et al. (2019)
(8) Disturbed protein folding and processing in ER	Acetate induces endoplasmic reticulum (ER) stress and triggers the unfolded protein response (UPR). Additionally, intracellular acidification leads to protein denaturation	Dong et al. (2017), Kawazoe et al. (2017)
(9) Mitochondrial dysfunction	Acetic acid exposure causes acidification of the mitochondrial matrix and induces mitochondrial structural alterations and degradation	Rego et al. (2012), Dong et al. (2017)
(10) Perturbation of iron homeostasis	Acetic acid stress exposure leads to increased expression of genes involved in iron uptake, translocation of Aft1 to the nucleus (Fig. 2), and elevated intracellular iron levels	Kawahata et al. (2006), Mira et al. (2010b), Martins et al. (2018)
(11) Decrease in ergosterol levels	Exposure to acetic acid stress leads to a decrease in ergosterol levels and induces the expression of genes involved in ergosterol biosynthesis and PDR18, which encodes a PM ABC transporter essential for preserving optimal ergosterol levels in the PM (Fig. 2)	Lindberg et al. (2013), Godinho et al. (2018), Ribeiro et al. (2022)
(12) Perturbation of sphingolipid balance	Acetic acid stress induces alterations in sphingolipid content, affecting cell fate, protein trafficking, signaling pathways and membrane permeability	Rego et al. (2012, 2018)
(13) Increase in plasma membrane nonspecific permeability	Exposure to acetic acid destabilizes the PM, disrupting proper selective permeability. As a response mechanism, alterations of plasma membrane lipid composition restrict the passive diffusion of lipophilic toxic compounds into the cell (Fig. 2)	Godinho et al. (2018), Ribeiro et al. (2022)