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Skeletal muscle, autophagy, and physical activity: the ménage à trois of metabolic regulation in health and disease

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Abstract

Metabolic homeostasis is essential for cellular survival and proper tissue function. Multi-systemic metabolic regulation is therefore vital for good health. A number of tissues have the task of maintaining appropriate metabolism, and skeletal muscle is the most abundant of them. Muscle possesses a remarkable plasticity and is able to rapidly adapt to changes in energetic demands by fine-tuning the balance between catabolic and anabolic processes. Autophagy is a catabolic process responsible for the degradation of protein aggregates and damaged organelles, through the autophagosome–lysosome system. Proper regulation of autophagy flux is fundamental for organism homeostasis under physiological conditions and even more in response to metabolic stress, such as during physical activity and nutritional deficits. Both deficient and excessive autophagy are harmful for health and have devastating consequences in a myriad of pathologies. The regulation of autophagy flux in various tissues, and in particular in skeletal muscle, is of great importance for health and tissue homeostasis and represents a feasible mechanism by which physical exercise exerts its beneficial effects on muscle and whole body metabolism. This review is focused on the key molecular mechanisms regulating macromolecule and organelle turnover in muscle during alterations in nutrient availability and energetic demands, as well as their involvement in disease pathogenesis.

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Acknowledgments

The authors apologize to their colleagues whose studies were not cited owing to space limitations. This work is supported by grants from Telethon-Italy (GGP10225 and GGP11082 to P.B.; TCP04009 to M.S), the European Union (MYOAGE, contract: 223576 of FP7 to M.S.; BIO-NMD FP7-HEALTH-241665 to P.B.), ERC (MYOPHAGY, contract: 282310 to M.S.), the Italian Ministry of Education, University and Research (to P.B. and M.S.), Foundation Leducq (to M.S.), and CARIPARO (to M.S. and P.B.). A.V. is supported by scholarships from Natural Sciences and Engineering Research Council of Canada-CGS and NSERC Michael Smith Foreign Study Supplement. The authors declare no conflict of interest.

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Authors and Affiliations

  1. School of Kinesiology and Health Science, York University, Toronto, Canada

    Anna Vainshtein

  2. Department of Molecular Medicine, University of Padova, Padova, Italy

    Paolo Grumati & Paolo Bonaldo

  3. Department of Biomedical Sciences, University of Padova, Padova, Italy

    Marco Sandri

  4. Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, 35129, Padova, Italy

    Marco Sandri

  5. Department of Medicine, McGill University, Montreal, Canada

    Marco Sandri

  6. Muscle Health Research Center, York University, Toronto, Canada

    Anna Vainshtein

  7. Telethon Institute of Genetics and Medicine (TIGEM), 80131, Napoli, Italy

    Marco Sandri

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  1. Anna Vainshtein
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  2. Paolo Grumati
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  4. Paolo Bonaldo
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Correspondence to Marco Sandri or Paolo Bonaldo.

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Anna Vainshtein and Paolo Grumati equally contributed to this work.

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Vainshtein, A., Grumati, P., Sandri, M. et al. Skeletal muscle, autophagy, and physical activity: the ménage à trois of metabolic regulation in health and disease. J Mol Med 92, 127–137 (2014). https://doi.org/10.1007/s00109-013-1096-z

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