title: Inhibition of autophagosome formation restores mitochondrial function in mucolipidosis II and III skin fibroblasts.
abstract: Mucolipidosis II and III are progressive lysosomal storage disorders caused by a deficiency of N-acetylglucosamine-1-phosphotransferase, leading to massive accumulation of undigested substrates in lysosomes (inclusion bodies) in skin fibroblast. In this study, we demonstrated accumulation of autolysosomes and increased levels of p62 and ubiquitin proteins in cultured fibroblasts. These autophagic elevations were milder in mucolipidosis III compared with mucolipidosis II. Mitochondrial structure was fragmented and activity was impaired in the affected cells, and 3-methyladenine, an inhibitor of autophagosome formation, restored these. These results show for the first time autophagic and mitochondrial dysfunctions in this disorder.
authors: Department of Pediatrics (D-5), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Takanobu
authors: T
authors: Otomo
authors: Katsumi
authors: K
authors: Higaki
authors: Eiji
authors: E
authors: Nanba
authors: Keiichi
authors: K
authors: Ozono
authors: Norio
authors: N
authors: Sakai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001343:Autophagy; D002401:Cathepsin B / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*; D009081:Mucolipidoses / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D010588:Phagosomes / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D000071456:Sequestosome-1 Protein; D012867:Skin / Q000473:pathology*; D013347:Subcellular Fractions / Q000201:enzymology; D057149:Ubiquitinated Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D057149:Ubiquitinated Proteins; D002401:Cathepsin B; D002402:Cathepsin D