COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation

• Published in: Cell reports (Cambridge) Vol. 16; no. 9; pp. 2387 - 2398
• Main Authors: Pérez-Pérez, Rafael, Lobo-Jarne, Teresa, Milenkovic, Dusanka, Mourier, Arnaud, Bratic, Ana, García-Bartolomé, Alberto, Fernández-Vizarra, Erika, Cadenas, Susana, Delmiro, Aitor, García-Consuegra, Inés, Arenas, Joaquín, Martín, Miguel A., Larsson, Nils-Göran, Ugalde, Cristina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30-08-2016; Elsevier
• Subjects: Animals; Electron Transport; Electron Transport Complex I - genetics; Electron Transport Complex I - metabolism; Electron Transport Complex III - genetics; Electron Transport Complex III - metabolism; Electron Transport Complex IV - genetics; Electron Transport Complex IV - metabolism; Gene Expression; HEK293 Cells; HeLa Cells; Humans; Medicin och hälsovetenskap; Mice; Mitochondria, Heart - chemistry; Mitochondria, Heart - metabolism; Mitochondrial Membranes - metabolism; Myocardium - cytology; Myocardium - metabolism; Oxidative Phosphorylation; Protein Binding; Protein Stability
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.07.081

Mitochondrial respiratory chain (MRC) complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian respiratory chain. As in the mouse, human COX7A2L binds primarily to free mitochondrial complex III and, to a minor extent, to complex IV to specifically promote the stabilization of the III2+IV supercomplex without affecting respirasome formation. Furthermore, COX7A2L does not affect the biogenesis, stabilization, and function of the individual oxidative phosphorylation complexes. These data show that independent regulatory mechanisms for the biogenesis and turnover of different MRC supercomplex structures co-exist.
[Display omitted]
•COX7A2L preferentially interacts with respiratory chain complex III•COX7A2L is essential to stabilize the III2+IV supercomplex•COX7A2L is not necessary for biogenesis or maintenance of the respirasome•Biogenesis of the III2+IV supercomplex is not necessary for respirasome formation
Previous studies highlight different roles for COX7A2L in the structural organization of the mitochondrial respiratory chain. Pérez-Pérez et al. find that mammalian COX7A2L preferentially associates with complex III to stabilize supercomplex III2+IV in a respirasome-independent manner, indicating coexistence of independent regulatory mechanisms for the biogenesis and turnover of these structures.