title: Mitochondrial dynamic remodeling in strenuous exercise-induced muscle and mitochondrial dysfunction: regulatory effects of hydroxytyrosol.
abstract: Physical exercise is considered to exert a positive effect on health, whereas strenuous or excessive exercise (Exe) causes fatigue and damage to muscle and immune functions. The underlying molecular mechanisms are still unclear. We designed a protocol to mimic Exe and explore the ensuing cellular damage and involvement of mitochondrial dynamics. We found that Exe was prone to decrease endurance capacity and induce damage to renal function and the immune system. Muscle atrophy markers atrogin-1 and MuRF1 mRNA were increased by Exe, accompanied by increased autophagy and mitochondrial fission in skeletal muscle. Exe caused a decrease in PGC-1α and complex I expression; it also activated JNK and Erk1/2 pathways and consequently induced p53, p21, and MnSOD expression in skeletal muscle. The involvement of oxidant-induced autophagy and mitochondrial dysfunction was confirmed in C2C12 myoblasts. Hydroxytyrosol (HT), a natural olive polyphenol, efficiently enhanced endurance capacity and prevented Exe-induced renal and immune system damage. Also, HT treatment inhibited both the Exe-induced increase in autophagy and mitochondrial fission and the decrease in PGC-1α expression. In addition, HT enhanced mitochondrial fusion and mitochondrial complex I and II activities in muscle of Exe rats. These results demonstrate that Exe-induced fatigue and damage to muscle and immune functions may be mediated via the regulation of mitochondrial dynamic remodeling, including the downregulation of mitochondrial biogenesis and upregulation of autophagy. HT supplementation may regulate mitochondrial dynamic remodeling and enhance antioxidant defenses and thus improve exercise capacity under Exe conditions.
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Feng
authors.forename: Liyuan
authors.initials: L
authors.lastname: Bai
authors.forename: Jiong
authors.initials: J
authors.lastname: Yan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Weili
authors.initials: W
authors.lastname: Shen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Karin
authors.initials: K
authors.lastname: Wertz
authors.forename: Peter
authors.initials: P
authors.lastname: Weber
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000276:immunology*; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol