Autophagy and mitochondria in Pompe disease: Nothing is so new as what has long been forgotten

Authors

  • Nina Raben,

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    • 50 South Drive Bld.50/1345 NIAMS, NIH, Bethesda, MD 20892-1820.
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    • Nina Raben is a Staff Scientist at the Laboratory of Muscle Stem Cells and Gene Regulation (NIAMS, NIH). Her scientific interests have centered on Pompe disease, in particular, on the role of autophagy in the pathogenesis of the disorder.

  • Amanda Wong,

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    • Amanda Wong was formerly a postbaccalaureate fellow at the NIAMS, NIH, where she investigated the role of autophagy in murine Pompe disease. She is currently an M.D./Ph.D. candidate at the University of Michigan.

  • Evelyn Ralston,

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    • Evelyn Ralston is head of the Light Imaging Section in the Office of Science and Technology, NIAMS, NIH. Her group focuses on the organization of microtubules and their associated organelles in skeletal muscle.

  • Rachel Myerowitz

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    • Rachel Myerowitz was formerly a PI at NIDDK, NIH, where she studied lysosomal storage disorders. She is currently a professor of Biology at St. Mary's College of Maryland and a guest scientist at NIAMS, NIH.


  • How to cite this article: Raben N, Wong A, Ralston E, Myerowitz R. 2012. Autophagy and mitochondria in Pompe disease: Nothing is so new as what has long been forgotten. Am J Med Genet Part C Semin Med Genet 160C:13–21.

Abstract

Macroautophagy (often referred to as autophagy) is an evolutionarily conserved intracellular system by which macromolecules and organelles are delivered to lysosomes for degradation and recycling. Autophagy is robustly induced in response to starvation in order to generate nutrients and energy through the lysosomal degradation of cytoplasmic components. Constitutive, basal autophagy serves as a quality control mechanism for the elimination of aggregated proteins and worn-out or damaged organelles, such as mitochondria. Research during the last decade has made it clear that malfunctioning or failure of this system is associated with a wide range of human pathologies and age-related diseases. Our recent data provide strong evidence for the role of autophagy in the pathogenesis of Pompe disease, a lysosomal glycogen storage disease caused by deficiency of acid alpha-glucosidase (GAA). Large pools of autophagic debris in skeletal muscle cells can be seen in both our GAA knockout model and patients with Pompe disease. In this review, we will focus on these recent data, and comment on the not so recent observations pointing to the involvement of autophagy in skeletal muscle damage in Pompe disease. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

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