Poking a hole in mitochondria

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...