Biomolecules. 2025 Aug 22. pii: 1209. [Epub ahead of print]15(9):
The role of electron transport chain supercomplexes and factors that regulate their composition in a tissue- and species-specific manner are not fully understood. Tissue-specific isoforms have been reported for cytochrome c oxidase (COX), which may contribute to such regulation. Therefore, we here investigated COX activity and structural organization in wild-type (WT) and COX7A1 knockout (KO) mice, which lack the heart/skeletal muscle isoform of COX subunit VIIa. COX7A1 KO mice showed a 30% reduction in total COX activity in the heart. Although the activity of COX in the monomers and I+III2+IVn supercomplexes (SCs) remained unchanged, a marked reduction in COX dimers and unknown COX-containing species IVx and IVy contributed to the overall reduction in COX activity. Furthermore, we observed that COX7A2 substituted for COX7A1 in COX monomers, dimers, and all COX-containing SCs in the KO mice, indicating a compensatory mechanism to preserve COX functionality. Collectively, these results suggest that COX7A1 plays an important role in maintaining structural stability; however, they also suggest that loss of COX7A1 is compensated by its replacement with COX7A2.
Keywords: COX7aH; COX7aL; cytochrome c oxidase; heart; isoforms