Sci Adv. 2020 Jun;6(26): eaba7509
Enrique Calvo,
Sara Cogliati,
Pablo Hernansanz-Agustín,
Marta Loureiro-López,
Adela Guarás,
Rafael A Casuso,
Fernando García-Marqués,
Rebeca Acín-Pérez,
Yolanda Martí-Mateos,
J C Silla-Castro,
Marta Carro-Alvarellos,
Jesús R Huertas,
Jesús Vázquez,
J A Enríquez.
Mitochondrial respiratory complexes assemble into supercomplexes (SC). Q-respirasome (III2 + IV) requires the supercomplex assembly factor (SCAF1) protein. The role of this factor in the N-respirasome (I + III2 + IV) and the physiological role of SCs are controversial. Here, we study C57BL/6J mice harboring nonfunctional SCAF1, the full knockout for SCAF1, or the wild-type version of the protein and found that exercise performance is SCAF1 dependent. By combining quantitative data-independent proteomics, 2D Blue native gel electrophoresis, and functional analysis of enriched respirasome fractions, we show that SCAF1 confers structural attachment between III2 and IV within the N-respirasome, increases NADH-dependent respiration, and reduces reactive oxygen species (ROS). Furthermore, the expression of AOX in cells and mice confirms that CI-CIII superassembly segments the CoQ in two pools and modulates CI-NADH oxidative capacity.