UNIGE document Scientific Article
previous document  unige:21  next document
add to browser collection
Title

Bax activation and stress-induced apoptosis delayed by the accumulation of cholesterol in mitochondrial membranes

Authors
Published in Cell Death and Differentiation. 2008, vol. 15, p. 484-493
Abstract Activation of Bax or Bak is essential for the completion of many apoptotic programmes. Under cytotoxic conditions, these proteins undergo a series of conformational rearrangements that end up with their oligomerization. We found that unlike inactive monomeric Bax, active oligomerized Bax is partially resistant to trypsin digestion, providing a convenient read out to monitor Bax activation. Using this assay, we studied how the lipid composition of membranes affects tBid-induced Bax activation in vitro with pure liposomes. We report that Bax activation is inhibited by cholesterol and by decreases in membrane fluidity. This observation was further tested in vivo using the drug U18666A, which we found increases mitochondrial cholesterol levels. When incubated with tBid, mitochondria isolated from U18666A-treated cells showed a delay in the release of Smac/Diablo and Cytochrome c, as well as in Bax oligomerization. Moreover, pre-incubation with U18666A partially protected cells from stress-induced apoptosis. As many tumours display high mitochondrial cholesterol content, inefficient Bax oligomerization might contribute to their resistance to apoptosis-inducing agents.
Identifiers
PMID: 18084240
Full text
Structures
Citation
(ISO format)
LUCKEN-ARDJOMANDE, Safa, MONTESSUIT, Sylvie, MARTINOU, Jean-Claude. Bax activation and stress-induced apoptosis delayed by the accumulation of cholesterol in mitochondrial membranes. In: Cell Death and Differentiation, 2008, vol. 15, p. 484-493. doi: 10.1038/sj.cdd.4402280 https://archive-ouverte.unige.ch/unige:21

502 hits

271 downloads

Update

Deposited on : 2008-10-29

Export document
Format :
Citation style :