Down-regulation of the mitochondrial i-AAA protease Yme1L induces muscle atrophy via FoxO3a and myostatin activation.

Down-regulation of the mitochondrial i-AAA protease Yme1L induces muscle atrophy via FoxO3a and myostatin activation. J Cell Mol Med. 2019 Nov 14;: Authors: Lee YJ, Kim GH, Park SI, Lim JH Abstract Muscle atrophy is closely associated with many diseases, including diabetes and cardiac failure. Growing evidence has shown that mitochondrial dysfunction is related to muscle atrophy; however, the underlying mechanisms are still unclear. To elucidate how mitochondrial dysfunction causes muscle atrophy, we used hindlimb-immobilized mice. Mitochondrial function is optimized by balancing mitochondrial dynamics, and we observed that this balance shifted towards mitochondrial fission and that MuRF1 and atrogin-1 expression levels were elevated in these mice. We also found that the expression of yeast mitochondrial escape 1-like ATPase (Yme1L), a mitochondrial AAA protease was significantly reduced both in hindlimb-immobilized mice and carbonyl cyanide m-chlorophenylhydrazone (CCCP)-treated C2C12 myotubes. When Yme1L was depleted in myotubes, the short form of optic atrophy 1 (Opa1) accumulated, leading to mitochondrial fragmentation. Moreover, a loss of Yme1L, but not of LonP1, activated AMPK and FoxO3a and concomitantly increased MuRF1 in C2C12 myotubes. Intriguingly, the expression of myostatin, a myokine responsible for muscle protein degradation, was significantly increased by the transient knock-down of Yme1L. Taken together, our results ...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research