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Holding Onto Two Jobs

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Science  07 Apr 2006:
Vol. 312, Issue 5770, pp. 22
DOI: 10.1126/science.312.5770.22c

Proteins in the Bcl-2 family are critical for programmed cell death (apoptosis). In mammals, pro-apoptotic proteins (such as Bax) stimulate mitochondrial fragmentation and the release of cytochrome c; anti-apoptotic proteins (such as Bcl-2 and Bcl-xL) oppose these processes. In the nematode Caenorhabditis elegans, CED-9, a protein related to Bcl-2, sequesters the caspase-activating protein CED-4 and thereby inhibits apoptosis. Delivani et al. expressed CED-9 in mammalian cells and found that, though localized to mitochondria, it failed to inhibit Bax-induced release of cytochrome c from mitochondria or apoptosis. However, CED-9 promoted remodeling of the mitochondrial network into large perinuclear structures and inhibited the mitochondrial fragmentation associated with apoptosis. EGL-1, which binds to CED-9, promoted mitochondrial fragmentation in mammalian cells (as it does in C. elegans) and inhibited CED-9-mediated mitochondrial fusion. When coexpressed in mammalian cells, CED-9 bound to mitofusin, a protein that promotes mitochondrial fusion. Similarly, Bcl-xL bound to mitofusin when cotransfected into mammalian cells and promoted mitochondrial fusion. The authors suggest that Bcl-2 family proteins are involved in regulating mitochondrial fission and fusion in addition to their role in regulating apoptosis. — EMA

Mol. Cell 21, 761 (2006).

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