Dear Editor,

Bcl-2 family members play pivotal roles in regulation of apoptosis. They functionally and physically associate with the mitochondrial membrane and regulate mitochondria-mediated apoptotic signals either positively or negatively. The proapoptotic Bcl-2 subfamily can be divided into two groups. One possesses multiple domains, that is, three Bcl-2 homology domains 1–3 (BH1–3) and the other possesses a BH3 domain alone.1, 2 To date, at least eight BH3-only protein members (Bad, Bid, Bik/Blk, Bim/Bod, Bmf, Hrk, PUMA and Noxa) have been identified and all of them strongly induce apoptosis. Their proapoptotic activity is strictly controlled by transcriptional or post-translational regulation. For example, transcription of Noxa and Puma is activated in a p53-dependent manner, whereas Bad, Bim and Bmf are regulated by phosphorylation. Although Bim and Bmf directly bind to DLC (dynein light-chain) proteins, which are components of both dynein and myosin V motor complexes, they are sequestered from DLC proteins when they are phosphorylated.3, 4, 5 These unbound Bim and Bmf molecules are recruited to the mitochondrial membrane and interact with Bcl-2 or Bcl-XL, allowing inhibition of their antiapoptotic activity.6

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