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

Abstract

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 CIV₂ 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.

Keywords: Ca(2+) signaling; cox7a1; cox7a2l; electron transport chain; heart regeneration; metabolic rewiring; mitochondria; muscle physiology; scaf1; supercomplex assembly; zebrafish.