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

• DOI: 10.1016/j.celrep.2023.113626
• Publication Date: 2023-12-28T17:49:10Z
• Authors: Jin Ma; Ping-yuan Wang; Jie Zhuang; Annie Y. Son; Alexander K. Karius; Abu Mohammad Syed; Masahiro Nishi; Zhichao Wu; Mateus P. Mori; Young-Chae Kim; Paul M. Hwang
• Keywords: Mediator

Exercise training can stimulate the formation of fatty-acid-oxidizing slow-twitch skeletal muscle fibers, which are inversely correlated with obesity, but molecular mechanism underlying this transformation requires further elucidation. Here, we report that downregulation mitochondrial disulfide relay carrier CHCHD4 by exercise decreases import TP53-regulated inhibitor apoptosis 1 (TRIAP1) into mitochondria, reduce cardiolipin levels and promote VDAC oligomerization in muscle. oligomerization, known to facilitate mtDNA release, activate cGAS-STING/NFKB innate immune signaling downregulate MyoD muscle, thereby promoting oxidative fibers. In mice, haploinsufficiency is sufficient pathway, leading increased fibers decreased fat accumulation aging. The identification a specific mediator regulating fiber provides an opportunity understand underpinnings complex metabolic conditions such as obesity could have therapeutic implications.