CHCHD4-TRIAP1 regulation of innate immune signaling mediates skeletal muscle adaptation to exercise.

ABSTRACT: Exercise training can stimulate the formation of fatty-acid-oxidizing slow-twitch skeletal muscle fibers, which are inversely correlated with obesity, but the molecular mechanism underlying this transformation requires further elucidation. Here, we report that the downregulation of the mitochondrial disulfide relay carrier CHCHD4 by exercise training decreases the import of TP53-regulated inhibitor of apoptosis 1 (TRIAP1) into mitochondria, which can reduce cardiolipin levels and promote VDAC oligomerization in skeletal muscle. VDAC oligomerization, known to facilitate mtDNA release, can activate cGAS-STING/NFKB innate immune signaling and downregulate MyoD in skeletal muscle, thereby promoting the formation of oxidative slow-twitch fibers. In mice, CHCHD4 haploinsufficiency is sufficient

SUBMITTER: Ma J 

PROVIDER: S-EPMC10851177 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature