| First Author | Yasuda T | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 5 | Pages | 112434 |
| PubMed ID | 37097817 | Mgi Jnum | J:335873 |
| Mgi Id | MGI:7485657 | Doi | 10.1016/j.celrep.2023.112434 |
| Citation | Yasuda T, et al. (2023) Mitochondrial dynamics define muscle fiber type by modulating cellular metabolic pathways. Cell Rep 42(5):112434 |
| abstractText | Skeletal muscle is highly developed after birth, consisting of glycolytic fast-twitch and oxidative slow-twitch fibers; however, the mechanisms of fiber-type-specific differentiation are poorly understood. Here, we found an unexpected role of mitochondrial fission in the differentiation of fast-twitch oxidative fibers. Depletion of the mitochondrial fission factor dynamin-related protein 1 (Drp1) in mouse skeletal muscle and cultured myotubes results in specific reduction of fast-twitch muscle fibers independent of respiratory function. Altered mitochondrial fission causes activation of the Akt/mammalian target of rapamycin (mTOR) pathway via mitochondrial accumulation of mTOR complex 2 (mTORC2), and rapamycin administration rescues the reduction of fast-twitch fibers in vivo and in vitro. Under Akt/mTOR activation, the mitochondria-related cytokine growth differentiation factor 15 is upregulated, which represses fast-twitch fiber differentiation. Our findings reveal a crucial role of mitochondrial dynamics in the activation of mTORC2 on mitochondria, resulting in the differentiation of muscle fibers. |
