Xu 2022 Nat Commun
Xu Z, Fu T, Guo Q, Zhou D, Sun W, Zhou Z, Chen X, Zhang J, Liu L, Xiao L, Yin Y, Jia Y, Pang E, Chen Y, Pan X, Fang L, Zhu MS, Fei W, Lu B, Gan Z (2022) Disuse-associated loss of the protease LONP1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength. https://doi.org/10.1038/s41467-022-28557-5 |
Β» Nat Commun 13:894. PMID: 35173176 Open Access
Xu Zhisheng, Fu Tingting, Guo Qiqi, Zhou Danxia, Sun Wanping, Zhou Zheng, Chen Xinyi, Zhang Jingzi, Liu Lin, Xiao Liwei, Yin Yujing, Jia Yuhuan, Pang Erkai, Chen Yuncong, Pan Xin, Fang Lei, Zhu Min-Sheng, Fei Wenyong, Lu Bin, Gan Zhenji (2022) Nat Commun
Abstract: Mitochondrial proteolysis is an evolutionarily conserved quality-control mechanism to maintain proper mitochondrial integrity and function. However, the physiological relevance of stress-induced impaired mitochondrial protein quality remains unclear. Here, we demonstrate that LONP1, a major mitochondrial protease resides in the matrix, plays a role in controlling mitochondrial function as well as skeletal muscle mass and strength in response to muscle disuse. In humans and mice, disuse-related muscle loss is associated with decreased mitochondrial LONP1 protein. Skeletal muscle-specific ablation of LONP1 in mice resulted in impaired mitochondrial protein turnover, leading to mitochondrial dysfunction. This caused reduced muscle fiber size and strength. Mechanistically, aberrant accumulation of mitochondrial-retained protein in muscle upon loss of LONP1 induces the activation of autophagy-lysosome degradation program of muscle loss. Overexpressing a mitochondrial-retained mutant ornithine transcarbamylase (ΞOTC), a known protein degraded by LONP1, in skeletal muscle induces mitochondrial dysfunction, autophagy activation, and cause muscle loss and weakness. Thus, these findings reveal a role of LONP1-dependent mitochondrial protein quality-control in safeguarding mitochondrial function and preserving skeletal muscle mass and strength, and unravel a link between mitochondrial protein quality and muscle mass maintenance during muscle disuse.
β’ Bioblast editor: Plangger M β’ O2k-Network Lab: CN Nanjing Gan Z
Labels: MiParea: Respiration, Genetic knockout;overexpression
Organism: Mouse
Tissue;cell: Skeletal muscle
Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET
Pathway: N, S, ROX
HRR: Oxygraph-2k
CN, 2022-12