Cytochrome c and mitochondrial dysfunction in AA-PCD pathways. At extracellular acidic pH values acetic acid enters yeast cells and dissociates into acetate and protons causing intracellular acidification. In NAC-sensitive AA-PCD (red dashed arrows) hydrogen peroxide (H₂O₂) accumulates early, superoxide dismutase (SOD) activity increases, while catalase activity is undetectable; cyt c is released to the cytosol in a YCA1-dependent manner as a functional protein, acting as an electron donor (c_red) to the electron transport chain and as a superoxide anion (O₂^-.) scavenger; in a late phase, mitochondrial functions progressively decline, as revealed by a decrease in mitochondrial membrane potential (ΔΨ), respiratory control index (RCI), and cyt c oxidase (COX) activity. Caspase-like activity increases and DNA fragmentation occurs. The NAC-insensitive (blue dashed arrows) AA-PCD takes place in a YCA1-independent manner without cyt c release, yet caspase-like activation and DNA fragmentation occur in a late phase. In cells expressing a catalytically inactive form of iso-1-cyt c (C_W65S; green dashed arrows), no release of mutant cyt c occurs with inhibition of AA-PCD, and there is a decrease in H₂O₂ production. Possible involvement of certain signaling pathways in the interplay between PCD and cell adaptation is also shown: intracellular acidification caused by AA-PCD induction may stimulate RAS–cAMP–PKA signaling pathway, causing mitochondrial dysfunction, which can activate retrograde (RTG) pathway. The RTG pathway is positively and negatively regulated by Ras and TOR pathways, respectively. The TOR pathway is found at the crossroad of AA-PCD and RTG signaling, which may play a role in AA-PCD resistance.