Scaf1 promotes respiratory supercomplexes and metabolic efficiency in zebrafish

Abstract

The oxidative phosphorylation (OXPHOS) system is a dynamic system in which the respiratory complexes coexist with superassembled quaternary structures called supercomplexes (SCs). The physiological role of SCs is still disputed. Here, we used zebrafish to study the relevance of respiratory SCs. We combined immunodetection analysis and deep data-independent proteomics to characterize these structures and found similar SCs to those described in mice, as well as novel SCs including III2 + IV2, I + IV, and I + III2 + IV2. To study the physiological role of SCs, we generated two null allele zebrafish lines for supercomplex assembly factor 1 (scaf1). scaf1 / fish displayed altered OXPHOS activity due to the disrupted interaction of complexes III and IV. scaf1 / fish were smaller in size and showed abnormal fat deposition and decreased female fertility. These physiological phenotypes were rescued by doubling the food supply, which correlated with improved bioenergetics and alterations in the metabolic gene expression program. These results reveal that SC assembly by Scaf1 modulates OXPHOS efficiency and allows the optimization of metabolic resources.Microscopy Imaging Center of the University of BernSpanish Ministry of Economy and Competitiveness, MINECO SAF2015-65633-RSpanish Ministry of Economy and Competitiveness, MINECO SAF2015-65633-RHuman Frontier Science Program RGP0016/2018European Research Council (ERC) 337703SNF 31003A-159721Swiss National Science Foundation (SNSF) 320030_170062MINECO BIO2015-67580-PCarlos III Institute of Health-Fondo de Investigacion Sanitaria) PRB3 IPT17/0019Fundacion La Marato TV3La Caixa Foundation HR17-00247Ministry of Economy, Industry and Competitiveness (MEIC)Pro-CNIC FoundationSevero Ochoa Center of Excellence (MEIC award) SEV-2015-050