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Caspase-8 (red) normally homes in on mitochondria (green) but diffuses widely when mature cardiolipin is absent (right).

Before they can get down to killing a cell, apoptosis-promoting caspase-8 enzymes must socialize. Gonzalvez et al. reveal that a mitochondrial lipid provides a gathering place where the enzymes can mingle.

After receiving an external death signal, cells can commit suicide in several ways. In one mechanism, inactive copies of caspase-8 gather at the death-inducing signaling complex (DISC) on the cell membrane. There, the molecules combine and cut one another, becoming active enzymes.

But in an alternative mechanism, Gonzalvez et al. showed that caspase-8 migrates to the mitochondria instead of combining at the DISC. While probing the function of cardiolipin, a mitochondrial membrane lipid, Gonzalvez et al. discovered how caspase-8 molecules meet up at this organelle.

The researchers tested cells from patients with Barth syndrome, a rare genetic disorder in which the functional form of cardiolipin is scarce. The cells survived treatment with apoptosis-triggering molecules such as TNF. Without mature cardiolipin, caspase-8 doesn't embed in the mitochondrial membrane and doesn't get activated, the scientists found.

Cardiolipin seems to serve as the mitochondrial equivalent of the DISC, a platform where caspase-8 molecules can collect and undergo the modifications necessary for activation. Still unclear is what signal directs caspase-8 to the mitochondria and whether other caspases also travel to the organelles to be switched on.

Gonzalvez, F., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200803129.[Abstract/Free Full Text]

Mitch Leslie

mitchleslie{at}comcast.net

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This Article Full Text (PDF, 729K) 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 Google Scholar Articles by Leslie, M. PubMed Articles by Leslie, M. Social Bookmarking                      What's this?