Key result
Deficiency in Yme1L and the consequential imbalance in mitochondrial dynamics result in the activation of FoxO3a and myostatin, contributing to muscle atrophy in mice and myotube models.
Why the study?
Mitochondrial dysfunction is linked to muscle atrophy in diseases like cardiac failure and diabetes, but the underlying mechanisms remain unclear.
Deficiency in the mitochondrial protease Yme1L induces an imbalance in mitochondrial dynamics, activating FoxO3a and myostatin to promote muscle atrophy.
Answers are grounded in this paper and cite their sources.
Mitochondrial fission-MuRF1 signaling may drive atrophy in cardiac failure; leaves open therapeutic targeting pending human validation.
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 suggest that a deficiency in Yme1L and the consequential imbalance in mitochondrial dynamics result in the activation of FoxO3a and myostatin, which contribute to the pathological state of muscle atrophy.
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Lee et al. (2019) studied Muscle atrophy. Yme1L depletion and hindlimb immobilization was evaluated on Activation of FoxO3a and myostatin and mitochondrial fragmentation. Deficiency in Yme1L and the consequential imbalance in mitochondrial dynamics result in the activation of FoxO3a and myostatin, contributing to muscle atrophy in mice and myotube models.
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