Skeletal muscle mitochondrial remodeling in exercise and diseases

Gan, Zhenji; Fu, Tingting; Kelly, Daniel P.; Vega, Rick B.

doi:10.1038/s41422-018-0078-7

Cited by 186 publications

(152 citation statements)

References 189 publications

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“…At a cellular level, to alleviate sarcopenia is necessary to improve mitochondria number and turnover of contractile proteins and anti-oxidant enzymes [126]. A proper mitochondrial turnover is crucial in muscle adaptation to exercise given that abnormal proteostasis leads to loss of contractile proteins in aged muscles [127,128]. However, despite controlled physical activity, complete muscle restoration is impossible due to unavoidable oxidative deterioration of fast glycolytic fibers and enhanced expression of age-related genes insensitive to exercise benefit [129,130].…”

Section: Exercise-an Anti-aging Strategy That Preserves Mitochondriamentioning

confidence: 99%

Impact of Melatonin on Skeletal Muscle and Exercise

Stacchiotti

Favero

Rodella

2020

Cells

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Skeletal muscle disorders are dramatically increasing with human aging with enormous sanitary costs and impact on the quality of life. Preventive and therapeutic tools to limit onset and progression of muscle frailty include nutrition and physical training. Melatonin, the indole produced at nighttime in pineal and extra-pineal sites in mammalians, has recognized anti-aging, anti-inflammatory, and anti-oxidant properties. Mitochondria are the favorite target of melatonin, which maintains them efficiently, scavenging free radicals and reducing oxidative damage. Here, we discuss the most recent evidence of dietary melatonin efficacy in age-related skeletal muscle disorders in cellular, preclinical, and clinical studies. Furthermore, we analyze the emerging impact of melatonin on physical activity. Finally, we consider the newest evidence of the gut–muscle axis and the influence of exercise and probably melatonin on the microbiota. In our opinion, this review reinforces the relevance of melatonin as a safe nutraceutical that limits skeletal muscle frailty and prolongs physical performance.

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Section: Exercise-an Anti-aging Strategy That Preserves Mitochondriamentioning

confidence: 99%

Impact of Melatonin on Skeletal Muscle and Exercise

Stacchiotti

Favero

Rodella

2020

Cells

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“…7G, H), including an important cluster regulating fatty acid metabolism (e.g., ATP-citrate synthase (ACLY), mitochondrial trifunctional enzyme subunit (HADH)α, FASN and PDK4) and the citrate cycle (e.g., isocitrate dehydrogenase (IDH)2, succinate dehydrogenase (SDH)b) ( Fig. 7F), most of which are direct targets of PPARα (Boergesen et al, 2012;Gan et al, 2018). In line with the transcriptomic data, exclusive nighttime running-induced proteins are more scarce, and not attributable to specific pathways by KEGG analysis.…”

Section: Characterization Of the Muscle Transcriptome Proteome And Pmentioning

confidence: 99%

Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and Zeitgeber activity of endurance training

Maier

Delezie

Westermark

et al. 2020

Preprint

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Timed physical activity might potentiate the health benefits of training. The underlying signaling events triggered by exercise at different times of the day are, however, poorly understood. Here, we found that time-dependent variations in maximal treadmill exercise capacity of naive mice were associated with energy stores, mostly hepatic glycogen levels. Importantly, running at different times of the day resulted in a vastly different activation of signaling pathways, e.g., related to stress response, vesicular trafficking, repair, and regeneration. Second, voluntary wheel running at the opposite phase of the dark, feeding period surprisingly revealed minimal Zeitgeber (i.e., synchronizing) activity of training. This integrated study provides important insights into the circadian regulation of endurance performance and the control of the circadian clock by exercise. These results are of high importance to understand circadian aspects of training design in athletes and the application of chrono-exercise-based interventions in patients.

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“…Disrupted mitonuclear communication is implicated in metabolic diseases, cancer, neurodegeneration, and other aging processes [6,[53][54][55]. While little is known about mitonuclear signaling regulator in sarcopenia.…”

Section: Discussionmentioning

confidence: 99%

Loss of HtrA2/Omi protease activity induces mitonuclear imbalance and sarcopenia via differential regulation of mitochondrial biogenesis

Zhou

Yuan

Gao

et al. 2020

Preprint

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Background Cellular homeostasis requires tight coordination between nucleus and mitochondria, organelles that each possess their own genomes. Disrupted mitonuclear communication has been found to be implicated in many aging processes. However little is known about mitonuclear signaling regulator in sarcopenia which is a major contributor to the risk of poor health-related quality of life, disability and premature death in older people. HtrA2/Omi is a mitochondrial protease and play an important role in mitochondrial proteostasis. HtrA2 mnd2(-/-) mice harboring protease-deficient HtrA2/Omi Ser276Cys missense mutants exhibit premature aging phenotype. Additionally, HtrA2/Omi has been established as a signaling regulator in nervous system and tumors. We therefore asked whether HtrA2/Omi participates in mitonuclear signaling regulation in aging muscle.Methods Using motor functional, histological and molecular biological methods, we characterized the muscle phenotype of HtrA2 mnd2(-/-) mice. We employed bioinformatics analysis and identified HtrA2/Omi as a gene differentially associated with nDNA/mtDNA gene expression in sarcopenia. Further, we isolated the gastrocnemius muscle of HtrA2 mnd2(-/-) mice and determined expression of genes in UPR mt , mitohormesis, electron transport chain (ETC), and mitochondrial biogenesis.Results Here, we showed that HtrA2/Omi protease deficiency induced denervation-independent skeletal muscle degeneration. Despite of mitochondrial hypofunction, upregulation of UPR mt and mitohormesis related genes and elevated reactive oxygen species (ROS) production were not observed in HtrA2 mnd2(-/-) mice, contrary to previous assumptions that loss of protease activity of HtrA2/Omi would lead to mitochondrial dysfunction as a result of proteostasis disturbance and ROS burst. Instead, we showed that HtrA2/Omi protease deficiency results in different changes between the expression of nDNA and mtDNA encoded ETC subunits, which is in consistent with their transcription factors NRF-1/2 and coactivator PGC-1α, suggesting that HtrA2/Omi protease activity may differentially regulate mitonuclear signaling via mitochondrial biogenesis in sarcopenia. Besides, Akt1 but not GSK3β showed increased expression level in HtrA2 mnd2(-/-) muscles, indicating an involvement of Akt1 in PGC-1α regulation response to HtrA2/Omi protease deficiency.Conclusions HtrA2/Omi protease deficiency induces mitonuclear imbalance and sarcopenia via differential regulation of mitochondrial biogenesis. The novel mechanistic insights may be of importance in developing new therapeutic strategies for sarcopenia.

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Skeletal muscle mitochondrial remodeling in exercise and diseases

Cited by 186 publications

References 189 publications

Impact of Melatonin on Skeletal Muscle and Exercise

Impact of Melatonin on Skeletal Muscle and Exercise

Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and Zeitgeber activity of endurance training

Loss of HtrA2/Omi protease activity induces mitonuclear imbalance and sarcopenia via differential regulation of mitochondrial biogenesis

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