membrane, and it was also seen after intercalation of BH3-only proteins, which resulted in Bax activation [47]. Of note, this proapoptotic activity appeared as independent of the BH3 domain. Thus for the BH3-only protein Bnip3, the transmem- brane domain (TM) has been proven as essential for its proapoptotic activity, whereas BH3 could be mutated without major effect on apoptosis induction [48]. Also for BimS, deletion or point mutation of its BH3 on one hand prevented the interaction with Bcl-2 and Bax but remained largely without effect on apoptosis induction. BimS mutants still localized to mitochondria, suggesting that this was the critical step, and indeed, when the TM was deleted, the proapoptotic activity was lost [49]. Also for Bcl- xAK, mitochondrial translocation appeared as the critical step. A deletion analysis for Bcl-xAK may become particularly helpful for identification of proapoptotic domain(s) independent of BH3, as overlapping functions with BH3 are here excluded. 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