title: Autophagic dysfunction in a lysosomal storage disorder due to impaired proteolysis.
abstract: Alterations in macroautophagy (hereafter referred to as "autophagy") are a common feature of lysosomal storage disorders, and have been hypothesized to play a major role in the pathogenesis of these diseases. We have recently reported multiple defects in autophagy contributing to the lysosomal storage disorder Niemann-Pick type C (NPC). These include increased formation of autophagosomes, slowed turnover of autophagosomes secondary to impaired lysosomal proteolysis, and delivery of stored lipids to the lysosome via autophagy. The study summarized here describes novel methods for the interrogation of individual stages of the autophagic pathway, and suggests mechanisms by which lipid storage may result in broader lysosomal dysfunction.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Elrick
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lieberman
mesh_terms: D001343:Autophagy; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000473:pathology* / Q000503:physiopathology*; D008565:Membrane Proteins / Q000378:metabolism; D052556:Niemann-Pick Disease, Type C / Q000473:pathology / Q000503:physiopathology; D059748:Proteolysis
chemical_list: D008565:Membrane Proteins
keywords: Niemann-Pick; autophagy; cathepsin; cholesterol; lipid storage; lysosome; neurodegeneration