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Reorganization of Mitochondrial Respiratory Supercomplexes Induces Myoblasts Differentiation

ABSTRACT: The existence of respiratory supercomplexes (SCs) has been well acknowledged especially with the development of cryo-EM in the past few years, but their physiological relevance remains elusive. Dynamics of OXPHOS complexes is tightly correlated to cell fate switch, but whether SCs involve in this process is unknown. During C2C12 myogenesis, CIII2 and CIV as well as the subunits of CIII and CIV were slightly increasing, while SC III2+IV was decreasing, which indicates that SC reorganization may regulate myogenesis. Knockdown Cox7a2l decreased SCs III2+IV, I+III2+IV2 and I+III2+IV3, but had little effect on I+III2+IV. Transcriptome and quantitative-proteome analysis indicated that Cox7a2l silence activated myogenic gene expression and repressed cell cycle-associated gene expression. Besides, knockdown of Cox7a2l decreased CII abundance and accumulated succinate, which in turn suppressed certain key transcription factors, such as HMGA1 which is important for stemness maintenance. Our results indicated that respiratory supercomplex reorganization changed succinate homeostasis and myogenesis related gene expression profiles, thus switching cell fate.

ORGANISM(S): Mus musculus

PROVIDER: GSE178547 | GEO | 2021/11/01

REPOSITORIES: GEO

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