Autophagy and apoptosis in the oxidative stress protection of extracellular acidity

Purpose: This study aimed to investigate the impact of extracellular acidity on oxidative stress resistance and to explore the interplay between apoptosis and autophagy on Saccharomyces cerevisiae. Materials and Methods: Cells were cultured under either standard or acidic media and exposed to 8 mM hydrogen peroxide (H₂O₂) to induce oxidative stress. Cell viability, intracellular reactive oxygen species (ROS) levels, apoptotic cell ratio, and autophagolysosomes were evaluated by colony-forming unit (CFU) assay, fluorescence-based staining techniques, and microscopy. Mutant strains deficient in key genes in apoptosis and autophagy were utilized to evaluate specific contributions of these pathways to oxidative stress resistance. Results: Cells cultured in the acidic environment showed resistance to oxidative stress. The CFU fold change ratios after 30 minutes of exposure were increased from 0.031 to 0.181, ROS levels were reduced from 18.35% to 2.44%, apoptotic cell ratios were decreased from 21.06% to 12.45%, and autophagic activities were increased from 97.68 to 115.48. In mutant strains subjected to oxidative stress in acidic media, CFU fold change ratios were also higher in yca1Δ (0.172), atg4Δ (0.215), and atg8Δ (0.153) compared to wild-type cells (0.103), indicating that both apoptosis and autophagy pathways contribute to the oxidative stress response under acidic conditions. Conclusion: These findings provide novel insights into the influence of acidic microenvironments on cellular stress responses and may contribute to the development of therapeutic strategies for diseases associated with oxidative damage and tissue acidosis.