Cox7a2l, also known as Scaf1 or supercomplex assembly factor 1, is a supercomplex-specific assembly factor in mammals. It is involved in the formation of mitochondrial respiratory supercomplexes, which are crucial for efficient oxidative phosphorylation, a key metabolic pathway in cells [2,3,4,5]. These supercomplexes play a vital role in cellular metabolism, energy production, and overall cell function. Genetic models, such as knockout (KO) mouse models, have been instrumental in studying its function.

In mice, specific reconstitution of Cox7a2l expression in C57BL/6J mice leads 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. These findings suggest its importance in cardiorespiratory fitness [1]. In addition, depleting Cox7a2l in DBA/2J mice promotes the use of proteins/amino acids as oxidative carbon sources, revealing its role in metabolic regulation [4].

In conclusion, Cox7a2l is essential for the formation of mitochondrial supercomplexes, playing a significant role in cardiorespiratory fitness and metabolic regulation. Studies using KO mouse models have provided insights into its function, which could have implications for understanding and treating conditions related to metabolic and cardiovascular health [1,4].

References:

1. Benegiamo, Giorgia, Bou Sleiman, Maroun, Wohlwend, Martin, Eriksson, Johan G, Auwerx, Johan. 2022. COX7A2L genetic variants determine cardiorespiratory fitness in mice and human. In Nature metabolism, 4, 1336-1351. doi:10.1038/s42255-022-00655-0. https://pubmed.ncbi.nlm.nih.gov/36253618/

2. Balsa, Eduardo, Soustek, Meghan S, Thomas, Ajith, Enriquez, José Antonio, Puigserver, Pere. 2019. ER and Nutrient Stress Promote Assembly of Respiratory Chain Supercomplexes through the PERK-eIF2α Axis. In Molecular cell, 74, 877-890.e6. doi:10.1016/j.molcel.2019.03.031. https://pubmed.ncbi.nlm.nih.gov/31023583/

3. Lobo-Jarne, Teresa, Nývltová, Eva, Pérez-Pérez, Rafael, Ugalde, Cristina, Barrientos, Antoni. . Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics. In Cell reports, 25, 1786-1799.e4. doi:10.1016/j.celrep.2018.10.058. https://pubmed.ncbi.nlm.nih.gov/30428348/

4. Zhang, Kun, Chen, Linjie, Wang, Bo, Lyu, Jianxin, Fang, Hezhi. 2023. Mitochondrial supercomplex assembly regulates metabolic features and glutamine dependency in mammalian cells. In Theranostics, 13, 3165-3187. doi:10.7150/thno.78292. https://pubmed.ncbi.nlm.nih.gov/37351168/

5. Pérez-Pérez, Rafael, Lobo-Jarne, Teresa, Milenkovic, Dusanka, Larsson, Nils-Göran, Ugalde, Cristina. 2016. COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation. In Cell reports, 16, 2387-98. doi:10.1016/j.celrep.2016.07.081. https://pubmed.ncbi.nlm.nih.gov/27545886/