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© The Rockefeller University Press, 0021-9525/2002/11/539 $5.00
The Journal of Cell Biology, Volume 159, Number 4, 539-539

Poking a hole in mitochondria

Bax and Bid release dextrans from liposomes that contain cardiolipin (black bars). Newmeyer/Elsevier

Proapoptotic Bcl-2 proteins release death proteins such as cytochrome c by poking holes directly in mitochondria, according to Tomomi Kuwana, Donald D. Newmeyer (La Jolla Institute for Allergy and Immunology, San Diego, CA), and colleagues.

Earlier in vivo studies of the large protein family were stymied by the number of family members, and in vitro assays were inconclusive. The Newmeyer group has now successfully developed a minimal cell-free membrane model that behaves like mitochondrial outer membranes (OMMs). Adding recombinant Bid and Bax to the membranes allowed the exit of molecules over 100 times bigger than cytochrome c. With further minimalism, the authors showed that Bid and Bax also released large molecules from protein-free liposomes, as long as the liposomes contained cardiolipin, a signature mitochondrial lipid. Thus, Bax, Bid, and cardiolipin seem to be all a cell needs to induce mitochondria to spill their death-inducing guts. "That we can permeabilize membranes with Bid and Bax alone means we don't need to invoke any more complicated mechanism," says Newmeyer.

The mechanism of hole formation is probably not simple, however. Tetramers of Bax were sufficient for the release of the macromolecules, but a Bax tetramer would not form a conventional protein channel of adequate size. Newmeyer hypothesizes that the insertion of Bax into the OMM may cause a rearrangement in or change the curvature of lipids, particularly cardiolipin, such that Bax and the lipids might both line the newly made opening.

Reference:

Kuwana, T., et al. 2002. Cell. 1111:331–342.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 631K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?