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Lysosome-Mediated A...
Lysosome-Mediated Apoptosis is Associated with Cathepsin D-Specific Processing of Bid at Phe24,Trp48, and Phe183
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- Appelqvist, Hanna (author)
- Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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- Johansson, Ann-Charlotte (author)
- Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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- Linderoth, Emma (author)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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- Johansson, Uno (author)
- Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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- Antonsson, Bruno (author)
- Geneva Research Centre, Switzerland
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- Steinfeld, Robert (author)
- University of Medical Centre Gottingen, Germany
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- Kågedal, Katarina (author)
- Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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- Öllinger, Karin (author)
- Östergötlands Läns Landsting,Linköpings universitet,Experimentell patologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik
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(creator_code:org_t)
- Institute for Clinical Science, 2012
- 2012
- English.
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In: Annals of Clinical and Laboratory Science. - : Institute for Clinical Science. - 0091-7370 .- 1550-8080. ; 42:3, s. 231-242
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
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- Bax-mediated permeabilization of the outer mitochondrial membrane and release of apoptogenic factors into the cytosol are key events that occur during apoptosis. Likewise, apoptosis is associated with permeabilization of the lysosomal membrane and release of lysosomal cathepsins into the cytosol. This report identifies proteolytically active cathepsin D as an important component of apoptotic signaling following lysosomal membrane permeabilization in fibroblasts. Lysosome-mediated cell death is associated with degradation of Bax sequestering 14-3-3 proteins, cleavage of the Box activator Bid, and translocation of Box to mitochondria, all of which were cathepsin D-dependent. Processing of Bid could be reproduced by enforced lysosomal membrane permeabilization, using the lysosomotropic detergent O-methyl-serine dodecylamine hydrochloride (MSDH). We identified three cathepsin D-specific cleavage sites in Bid, Phe24, Trp48, and Phe183. Cathepsin D-cleaved Bid induced Bax-mediated release of cytochrome c from purified mitochondria, indicating that the fragments generated are functionally active. Moreover, apoptosis was associated with cytosolic acidification, thereby providing a more favorable environment for the cathepsin D-mediated cleavage of Bid. Our study suggests that cytosolic cathepsin D triggers Bax-mediated cytochrome c release by proteolytic activation of Bid.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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