Premium
P38α MAPK coordinates the activities of several metabolic pathways that together induce atrophy of denervated muscles
Author(s) -
Odeh Maali,
TamirLivne Yael,
Haas Tali,
Bengal Eyal
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15070
Subject(s) - denervation , autophagy , muscle atrophy , atrophy , medicine , oxidative stress , endocrinology , microbiology and biotechnology , glycolysis , biology , protein turnover , mitophagy , protein degradation , mitochondrion , p38 mitogen activated protein kinases , oxidative phosphorylation , myocyte , ubiquitin , protein kinase a , skeletal muscle , metabolism , kinase , biochemistry , protein biosynthesis , apoptosis , gene
Physiological or pathological muscle disuse/inactivity or loss of the neural‐muscular junction cause muscle atrophy. Atrophy‐inducing conditions cause metabolic oxidative stress in the muscle tissue, activation of the ubiquitin‐proteasome and of the autophagosome‐lysosome systems, enhanced removal of the damaged proteins and organelles, and loss of muscle mass and strength. The signaling pathways that control these catabolic processes are only partially known. In this study, we systematically analyzed the role of p38α mitogen‐activated protein kinase (MAPK) in denervation‐mediated atrophy. Mice with attenuated activity of p38α (p38 AF ) are partially protected from muscle damage and atrophy. Denervated (Den) muscles of these mutant mice exhibit reduced signs of oxidative stress, decreased unfolded protein response and lower levels of ubiquitinated proteins relative to Den muscles of control mice. Further, whereas autopahagy flux is inhibited in Den muscles of control mice, Den muscles of p38 AF mice maintain normal level of autophagy flux. Last, muscle denervation affects differently the energy metabolism of muscles in normal and mutant mice; whereas denervation appears to increase mitochondrial oxidative metabolism in control mice, it elevates anaerobic glycolytic metabolism in p38 AF mice. Our results indicate, therefore, that attenuation of p38α activity in mice protects Den muscles by reducing oxidative stress, lowering protein damage and improving the clearance of damaged mitochondria by autophagy.