Thursday, July 26, 2007

Does the proapototic protein BAX form a pore for cytochrome c translocation?

Bax is a protein normally residing in the cytosol. Upon stimulation, Bax translocates to the outer mitochondrial membrane triggering cytochrome c release and initiating the apoptotic death of the cell. The exact molecular mechanism by which Bax promotes cytochrome c release from the mitochondrial compartment is unknown. One hypothesis is that in response to the apoptotic stimulus, Bax changes its conformation oligomerizing in the outer mitochondrial membrane forming a large pore of sufficient diameter to permit cytochrome c release from the mitochondria. To investigate this possibility, recombinant human Bax is added to a planar lipid bilayer and the electrophysiological activity is recorded. We find that, under oligomerization promoting conditions, Bax forms characteristicaly large pores with high open probabilities. Kris Sheets, a graduate student from the LSU Health Science Center is studying the interactions of Bax pores with cytochome c.

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