粒体自噬
骨骼肌
串扰
内分泌学
线粒体
内科学
脂肪组织
生物
平衡
细胞生物学
自噬
医学
生物化学
细胞凋亡
物理
光学
作者
Tingting Fu,Zhisheng Xu,Lin Liu,Qiqi Guo,Hao Wu,Xijun Liang,Danxia Zhou,Liwei Xiao,Lei Liu,Yong Liu,Min‐Sheng Zhu,Quan Chen,Zhenji Gan
出处
期刊:Cell Reports
[Elsevier]
日期:2018-05-01
卷期号:23 (5): 1357-1372
被引量:105
标识
DOI:10.1016/j.celrep.2018.03.127
摘要
The quality of mitochondria in skeletal muscle is essential for maintaining metabolic homeostasis during adaptive stress responses. However, the precise control mechanism of muscle mitochondrial quality and its physiological impacts remain unclear. Here, we demonstrate that FUNDC1, a mediator of mitophagy, plays a critical role in controlling muscle mitochondrial quality as well as metabolic homeostasis. Skeletal-muscle-specific ablation of FUNDC1 in mice resulted in LC3-mediated mitophagy defect, leading to impaired mitochondrial energetics. This caused decreased muscle fat utilization and endurance capacity during exercise. Interestingly, mice lacking muscle FUNDC1 were protected against high-fat-diet-induced obesity with improved systemic insulin sensitivity and glucose tolerance despite reduced muscle mitochondrial energetics. Mechanistically, FUNDC1 deficiency elicited a retrograde response in muscle that upregulated FGF21 expression, thereby promoting the thermogenic remodeling of adipose tissue. Thus, these findings reveal a pivotal role of FUNDC1-dependent mitochondrial quality control in mediating the muscle-adipose dialog to regulate systemic metabolism.
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