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