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Killer protein Bax (green) only moves from the cytosol to mitochondria (red) when its pro-death teammate Bim (blue, bottom) is present.

A revision of competing ideas about programmed cell death is in order, according to results from Weber et al. (page 625). The work gets a step closer to nailing down the controversial role of the BH3-only family of proteins as playing offense on the pro-death team of apoptotic proteins, rather than defense against the opposing protective agents.

Three groups of apoptosis proteins control a cell's life-or-death fate: Bax/Bak (the executioners) and BH3-only proteins are pro-apoptotic, whereas a subset of Bcl-2 proteins are anti-apopototic. But researchers have had a hard time deciding how the BH3-only proteins, a group that includes Bim, factor into the equation. One side argues that BH3-only proteins bind to Bax/Bak directly to turn on these killing machines. Another line of thinking has the BH3-only proteins running interference for the killers by soaking up and neutralizing the protective Bcl-2 members.

Here, Weber and colleagues introduce clues that suggest a bit of rethinking may be in order. An inducible version of Bim showed that high levels of Bim caused death without coming into contact with Bcl-2 protectors. In yeast that lacked any Bcl-2 proteins, Bim still enhanced the death action of Bax. This enhancement appeared to work by helping Bax insert into the mitochondrial membrane—but without a direct interaction.

The authors speculate that the translocation of Bim and other BH3-only proteins into the mitochondrial membrane sets up their pro-death teammate Bax to join them there. In any event, neither the direct-binding model or the displacement model appears to explain entirely how these proteins play the game.

Kendall Powell

kendall2{at}nasw.org

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Bim_S-induced apoptosis requires mitochondrial localization but not interaction with anti-apoptotic Bcl-2 proteins

Arnim Weber, Stefan A. Paschen, Klaus Heger, Florian Wilfling, Tobias Frankenberg, Heike Bauerschmitt, Barbara M. Seiffert, Susanne Kirschnek, Hermann Wagner, and Georg Häcker
J. Cell Biol. 2007 177: 625-636. [Abstract] [Full Text] [PDF]

This Article PDF (Full Text) 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 Powell, K. Search for Related Content PubMed Articles by Powell, K. Related Collections Related Article Social Bookmarking                      What's this?