Mitochondrial Dynamics Crucial in Determining Muscle Fiber Type, Study Finds
In a recent study published in Cell Reports, researchers led by Naotada Ishihara from Osaka University, Japan, shed light on the intricate relationship between mitochondrial dynamics and muscle fiber type differentiation.
The study uncovered that the loss of mitochondrial fission, a process controlled by dynamin-related protein 1 (Drp1), specifically hampers the differentiation of fast-twitch muscle fibers. This finding challenges previous notions, emphasizing the pivotal role of mitochondrial dynamics in shaping muscle composition post-birth.
By depleting Drp1 in both mouse skeletal muscle and cultured myotubes, the researchers observed a distinct reduction in fast-twitch fibers, independent of respiratory function. This shift in fiber type was accompanied by the activation of the Akt/mammalian target of rapamycin (mTOR) pathway, facilitated by the accumulation of mTOR complex 2 (mTORC2) on elongated and bulb-like mitochondria.
Excitingly, intervention through rapamycin administration effectively rescued the decline in fast-twitch fibers both in vivo and in vitro, highlighting the potential for targeted therapies in muscle-related disorders.
Furthermore, the study identified the upregulation of growth differentiation factor 15 (GDF-15), a mitochondria-related cytokine, under Akt/mTOR activation. This upregulation, in turn, suppressed the differentiation of fast-twitch fibers, unraveling a previously unknown regulatory mechanism in muscle development.
Overall, these findings elucidate the critical role of mitochondrial dynamics in activating mTORC2 on mitochondria, ultimately dictating the differentiation of muscle fibers. The study not only enhances our understanding of muscle biology but also unveils potential avenues for therapeutic interventions in muscle-related pathologies.
