| Loss of the lysosomal ion channel TRPML1 leads to cathepsin B-dependent apoptosis. | |
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MedLine Citation:
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PMID: 22262857 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Mucolipidosis type IV (MLIV) is a lysosomal storage disease caused by mutations in the gene MCOLN1, which codes for the transient receptor potential family ion channel TRPML1. MLIV has an early onset and is characterized by developmental delays, motor and cognitive deficiencies, gastric abnormalities, retinal degeneration and corneal cloudiness. The degenerative aspects of MLIV have been attributed to cell death, whose mechanisms remain to be delineated in MLIV and in most other storage diseases. Here we report that an acute siRNA mediated loss of TRPML1 specifically causes a leak of lysosomal protease Cathepsin B (CatB) into the cytoplasm. CatB leak is associated with apoptosis, which can be prevented by CatB inhibition. Inhibition of proapoptotic protein Bax prevents TRPML1 KD mediated apoptosis but does not prevent cytosolic release of CatB. This is the first evidence providing mechanistic link between acute TRPML1 loss and cell death. |
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Authors:
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Grace A Colletti; Mark T Miedel; James Quinn; Neel Andharia; Ora A Weisz; Kirill Kiselyov |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-18 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Pittsburgh, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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