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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) superassembly, 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.
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Cox7a1 stabilizes CIV dimers.
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Impaired CIV dimer formation rewires skeletal and cardiac muscle metabolism.
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Loss of Cox7a1 impacts muscle physiology.
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Loss of Cox7a1 accelerates cardiac regeneration.
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Cox7a family members have specific functions on striated muscle physiology and injury response.