Roles of autophagy in slow-twitch skeletal muscle

为了评估自噬在骨骼肌萎缩中的作用，我们对骨骼肌特异性Atg7缺陷（Atg7 KO）小鼠进行去神经支配，这是一种骨骼肌萎缩模型。来自Atg7 KO小鼠的比目鱼肌（一种慢收缩骨骼肌）保持肌肉质量，而来自对照小鼠的比目鱼肌以及来自野生型和Atg7 KO小鼠的第一收缩肌肉萎缩。Atg7基因敲除小鼠失神经支配比目鱼肌中，线粒体活性降低，氧化应激积累，Parkin在线粒体中积累。帕金参与线粒体质量控制（帕金介导的线粒体自噬）。为了证实帕金介导的线粒体自噬是否参与Atg7 KO比目鱼肌中去神经萎缩的恢复，我们使帕金缺陷（帕金KO）小鼠去神经。与Atg7 KO Soleus一样，Parkin KO小鼠的失神经Soleus肌肉保持肌肉质量。这些结果表明，帕金介导的线粒体自噬参与失神经萎缩的慢收缩骨骼肌。

To evaluate the role of autophagy in skeletal muscle atrophy, we subjected skeletal muscle specific Atg7 deficient(Atg7 KO) mice to denervation, a model of skeletal muscle atrophy. Soleus muscle, a slow-twitch skeletal muscle, from Atg7 KO mice maintained muscle mass, while Soleus muscle from control mice, and first-twitch muscles from both wild type and Atg7 KO mice were atrophied. In the denervated Soleus muscles from Atg7 KO mice, the reduction of mitochondrial activity, the accumulation of oxidative stress and the accumulation of Parkin in mitochondria were observed. Parkin participates for mitochondrial quality control(Parkin mediated mitophagy). To confirm whether Parkin mediated mitophagy is involved in the restoration of denervation atrophy in Atg7 KO Soleus muscle, we subjected Parkin deficient(Parkin KO) mice to denervation. Like Atg7 KO Soleus, denervated Soleus muscles from Parkin KO mice maintained muscle mass. These results indicate that Parkin mediated mitophagy is involved in denervation atrophy in slow-twitch skeletal muscles.