title: Role of autophagy in glycogen breakdown and its relevance to chloroquine myopathy.
abstract: Several myopathies are associated with defects in autophagic and lysosomal degradation of glycogen, but it remains unclear how glycogen is targeted to the lysosome and what significance this process has for muscle cells. We have established a Drosophila melanogaster model to study glycogen autophagy in skeletal muscles, using chloroquine (CQ) to simulate a vacuolar myopathy that is completely dependent on the core autophagy genes. We show that autophagy is required for the most efficient degradation of glycogen in response to starvation. Furthermore, we show that CQ-induced myopathy can be improved by reduction of either autophagy or glycogen synthesis, the latter possibly due to a direct role of Glycogen Synthase in regulating autophagy through its interaction with Atg8.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zirin
authors.forename: Joppe
authors.initials: J
authors.lastname: Nieuwenhuis
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy; D020134:Catalytic Domain; D002738:Chloroquine; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050261:Glycogenolysis; D008247:Lysosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D020125:Mutation, Missense; D010588:Phagosomes / Q000201:enzymology
chemical_list: D029721:Drosophila Proteins; D002738:Chloroquine; D006003:Glycogen; D006006:Glycogen Synthase