Cox7a2l, also known as Scaf1 or SCAFI, is a supercomplex-specific assembly factor in mammals. Mitochondrial respiratory complexes form superassembled structures, and Cox7a2l is involved in facilitating the assembly of complex III and complex IV (CIII-CIV) super-assemblies, which impacts energetic efficiency [2]. It may also play a role in the biogenesis of certain supercomplexes and is part of the oxidative phosphorylation (OXPHOS) system in mitochondria. Genetic models, such as gene knockout mice, have been crucial in studying its function.

In C57BL/6J mice, specific reconstitution of Cox7a2l expression led to higher maximal oxygen consumption, increased lean mass, and increased energy expenditure. Also, Cox7a2l expression in mice is induced specifically in the muscle upon exercise, suggesting its role in cardiorespiratory fitness [1]. Depletion of Cox7a2l in DBA/2J mice promoted the use of proteins/amino acids as oxidative carbon sources, indicating its impact on metabolic pathways [3]. In C57BL/6 mice with a deletion in the Cox7a2l gene, supercomplex composition was altered in the liver, supporting a role for Cox7a2l in supercomplex assembly, though disease progression in Bcs1l mutant mice was unrelated to Cox7a2l isoforms [4].

In conclusion, Cox7a2l is essential for mitochondrial supercomplex formation and function. Studies using gene knockout mouse models have revealed its role in cardiorespiratory fitness and metabolic regulation. These findings have potential therapeutic implications, especially in reducing cardiovascular mortality [1].