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Article Addendum

Localized accumulation of oxidative stress causes muscle atrophy through activation of an autophagic pathway

Michela Aucello, Gabriella Dobrowolny and Antonio Musarò

A crucial system severely affected in different chronic diseases is the anti-oxidative defense, leading to accumulation of reactive oxygen species (ROS). The discovery that deletion in the anti-oxidant genes shortens significantly the mouse life span and that mutation in the major antioxidant enzyme SOD1 is associated with neurodegenerative diseases, has placed oxidative stress as a central mechanism in the pathogenesis of many pathological conditions. However, how such an oxidative insult plays a role in the diseases-related decrease of muscle performance and mass remains largely unknown. We recently demonstrated that autophagy plays a dominant role in the promotion of muscle atrophy associated with local alteration in the activity of the antioxidant enzyme SOD1. In particular, transcription of autophagy-related genes, such as those encoding LC3, Cathepsin-L and Bnip3, is activated in response to localized accumulation of oxidative stress and is mediated by FoxO3. In addition, our study documents how the T-tubule might be the potential donor of membrane that forms sequestering autophagic vesicles. Here we discuss the sequence of events leading to muscle atrophy.

Addendum to: Dobrowolny G, Aucello M, Rizzuto E, Beccafico S, Mammucari C, Bonconpagni S, Belia S, Wannenes F, Nicoletti C, Del Prete Z, Rosenthal N, Molinaro M, Protasi F, Fanò G, Sandri M, Musarò A. Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab 2008; 8:425-36; PMID: 19046573; DOI: 10.1016/j.cmet.2008.09.002.

Authors

Michela Aucello

Institute Pasteur Cenci-Bolognetti; Department of Histology and Medical Embryology; CE-BEMM and IIM; Sapienza University of Rome; Rome, Italy

Gabriella Dobrowolny

Institute Pasteur Cenci-Bolognetti; Department of Histology and Medical Embryology; CE-BEMM and IIM; Sapienza University of Rome; Rome, Italy

Antonio Musarò Corresponding author: antonio.musaro@uniroma1.it

Institute Pasteur Cenci-Bolognetti; Department of Histology and Medical Embryology; CE-BEMM and IIM; Sapienza University of Rome; Rome, Italy