Figure 4.

Function of c subunit in physiological and pathological mitochondria. The c subunit is encoded by three nuclear genes: ATP5G1, ATP5G2 and ATP5G3. Each of these genes, when translated, express the same mature sequence of the c subunit with differing signal peptides (A). Predictions based on the immature sequences of the c subunit isoforms indicate that the protein may be imported into mitochondria through the TIM/TOM complex (B). In physiological conditions (C), c subunit monomers fold into their native α-helical hairpin conformation and oligomerize into the c-ring of the ATPase. Conversely, in pathological conditions (E), the increased levels of Ca²⁺ influence the misfolding of the newly imported peptides causing them to oligomerize into a cross-β conformation (F) that contributes to PTP through permeabilizing the IMM (Created with Biorender.com).