Multistep and multitask Bax activation

Bax is a pro apoptotic protein allowing apoptosis to occur through the intrinsic damage induced pathway and amplifying that one occurring via the extrinsic receptor mediated pathway Bax is present in viable cells and activated by pro apoptotic stimuli Activation implies structural changes consisting of exposure of the N terminus and hydrophobic domains changes in localization consisting in migration from cytosol to mitochondria and endoplasmic rericulum membranes changes in the aggregation status from monomer to dimer and multimer Bax has multiple critical domains namely the N terminus exposed after activation two hydrophobic stretches exposed for membrane anchorage two reactive cystemes allowing multi-merization the BH3 domain for interactions with the Bcl 2 family members alpha helix 1 for t Bid interaction Box has also multiple functions It releases different mitochondrial factors such as cytochrome c SMAC/diablo it regulates mitochondrial fission the mitochondrial permeability transition pore it promotes Ca(2+) leakage through ER membrane Altogether Bax activation is a complex multi-step phenomenon Here we analyze these events as logically separable or alternative steps attempting to assess their role timing and reciprocal relation (C) 2010 Elsevier BV and Mitochondria Research Society All rights reserved