Abstract

Regulated removal of proteins and organelles by autophagy-lysosome system is critical for muscle homeostasis. Excessive activation of autophagy-dependent degradation contributes to muscle atrophy and cachexia. Conversely, inhibition of autophagy causes accumulation of protein aggregates and abnormal organelles, leading to myofiber degeneration and myopathy. Defects in lysosomal function result in severe muscle disorders such as Pompe (glycogen storage disease type II (GSDII)) disease, characterized by an accumulation of autophagosomes. However, whether autophagy is detrimental or not in muscle function of Pompe patients is unclear. We studied infantile and late-onset GSDII patients and correlated impairment of autophagy with muscle wasting. We also monitored autophagy in patients who received recombinant α-glucosidase. Our data show that infantile and late-onset patients have different levels of autophagic flux, accumulation of p62-positive protein aggregates and expression of atrophy-related genes. Although the infantile patients show impaired autophagic function, the late-onset patients display an interesting correlation among autophagy impairment, atrophy and disease progression. Moreover, reactivation of autophagy in vitro contributes to acid α-glucosidase maturation in both healthy and diseased myotubes. Together, our data suggest that autophagy protects myofibers from disease progression and atrophy in late-onset patients.

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Publisher Full Text

Authors

Nascimbeni AC, Fanin M, Masiero E, Angelini C, Sandri M

Institution

Department of Neurosciences, University of Padova, Biomedical Campus 'Pietro d'Abano', Italy.

Source

Cell death and differentiation 19:10 2012 Oct pg 1698-708

MeSH

Adaptor Proteins, Signal Transducing
Adult
Autophagy
Child
Enzyme Replacement Therapy
Female
Glycogen Storage Disease Type II
Humans
Male
Microtubule-Associated Proteins
Protein Binding
RNA-Binding Proteins
Recombinant Proteins
alpha-Glucosidases

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22595755