Back to Search
Start Over
Inhibition of autophagosome formation restores mitochondrial function in mucolipidosis II and III skin fibroblasts.
- Source :
-
Molecular genetics and metabolism [Mol Genet Metab] 2009 Dec; Vol. 98 (4), pp. 393-9. Date of Electronic Publication: 2009 Jul 07. - Publication Year :
- 2009
-
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.
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Autophagy
Cathepsin B metabolism
Cathepsin D metabolism
Fibroblasts enzymology
Humans
Inclusion Bodies metabolism
Lysosomes metabolism
Lysosomes pathology
Mucolipidoses enzymology
Phagosomes pathology
Protein Transport
Sequestosome-1 Protein
Subcellular Fractions enzymology
Ubiquitinated Proteins metabolism
Fibroblasts pathology
Mitochondria metabolism
Mucolipidoses pathology
Mucolipidoses physiopathology
Phagosomes metabolism
Skin pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-7206
- Volume :
- 98
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular genetics and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 19656701
- Full Text :
- https://doi.org/10.1016/j.ymgme.2009.07.002