Mitochondrial function is crucial for the regulation of energy metabolism, proton homeostasis, and stress adaptation in Saccharomyces cerevisiae . This study demonstrates the role of mitochondria in modulating cellular responses to varying extracellular pH (3.0, 5.0, 6.5) and glucose availability (0.5%, 2%). Results indicate that mitochondrial deficiencies in Δhap4 and ρ 0 mutants selectively impair growth under acidic pH and 0.5% glucose conditions, whereas wild-type cells maintain pH-independent growth. Mitochondrial impairment redistributes intracellular H + homeostasis regulation to plasma membrane and cytosolic H + -ATPases in a glucose- and pH-dependent manner, with ρ 0 cells exhibiting maximal reliance on non-mitochondrial ATPases. The N, N′ - dicyclohexylcarbodiimide (DCCD)-sensitive J H + scales inversely with glucose availability, reflecting energy demand under nutrient limitation and acid stress. ρ 0 cells exhibit the highest alcohol dehydrogenase activity to regulate the redox balance in response to non-functional mitochondria. The highest total H + -ATPase activity measured in ρ 0 cells at pH 6.5 and 0.5% glucose conditions, combined with proton flux data, indicates the upregulation of plasma membrane and cytosolic ATPases activity for maintaining proton motive force and intracellular pH due to a complete loss of F o F 1 -ATPase contribution. These results pave the way for the construction of robust S. cerevisiae yeast strains to varying glucose and extracellular pH conditions. • pH 3.0 and glucose limitation restrict growth of impaired mitochondria strains. • Mitochondria regulate proton homeostasis in yeast under glucose limitation. • Pma controls intracellular ATP and H + levels during mitochondrial dysfunctions. • 2% glucose alleviates mitochondria defects through fermentation and ADH activation. • ADH induction maintains redox balance to compensate for mitochondrial impairment.
Anikyan et al. (Fri,) studied this question.