Cox7a1 controls skeletal muscle physiology and heart regeneration through complex IV dimerization.

The oxidative phosphorylation (OXPHOS) system is intricately organized, with respiratory complexes forming super-assembled quaternary structures whose assembly mechanisms and physiological roles remain under investigation. Cox7a2l, also known as Scaf1, facilitates complex III and complex IV (CIII-CIV) super-assembly, enhancing energetic efficiency in various species. We examined the role of Cox7a1, another Cox7a family member, in supercomplex assembly and muscle physiology. Zebrafish lacking Cox7a1 exhibited reduced CIV 2 formation, metabolic alterations, and non-pathological muscle performance decline. Additionally, cox7a1 −/− hearts displayed a pro-regenerative metabolic profile, impacting cardiac regenerative response. The distinct phenotypic effects of cox7a1 −/− and cox7a2l −/− underscore the diverse metabolic and physiological consequences of impaired supercomplex formation, emphasizing the significance of Cox7a1 in muscle maturation within the OXPHOS system. [Display omitted] • Cox7a1 stabilizes CIV dimers • Impaired CIV dimer formation rewires skeletal and cardiac muscle metabolism • Loss of Cox7a1 impacts muscle physiology and heart regeneration • Cox7a1 and Cox7a2l loss of function lead to distinct alterations in striated muscle Complexes of the mitochondrial respiratory chain can assemble into supercomplexes (SCs). García-Poyatos et al. explore the role of Cox7a1 as a SC assembly factor and find that it controls mitochondrial respiration, influencing skeletal muscle physiology as well as cardiac injury response. [ABSTRACT FROM AUTHOR]