VDAC2 and the BCL-2 family of proteins.

Zheng Yuan, Grant Dewson, Peter E Czabotar, Richard W Birkinshaw

Biochemical Society transactions 2021 Dec 17

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The BCL-2 protein family govern whether a cell dies or survives by controlling mitochondrial apoptosis. As dysregulation of mitochondrial apoptosis is a common feature of cancer cells, targeting protein-protein interactions within the BCL-2 protein family is a key strategy to seize control of apoptosis and provide favourable outcomes for cancer patients. Non-BCL-2 family proteins are emerging as novel regulators of apoptosis and are potential drug targets. Voltage dependent anion channel 2 (VDAC2) can regulate apoptosis. However, it is unclear how this occurs at the molecular level, with conflicting evidence in the literature for its role in regulating the BCL-2 effector proteins, BAK and BAX. Notably, VDAC2 is required for efficient BAX-mediated apoptosis, but conversely inhibits BAK-mediated apoptosis. This review focuses on the role of VDAC2 in apoptosis, discussing the current knowledge of the interaction between VDAC2 and BCL-2 family proteins and the recent development of an apoptosis inhibitor that targets the VDAC2-BAK interaction. © 2021 The Author(s).

Citation

Zheng Yuan, Grant Dewson, Peter E Czabotar, Richard W Birkinshaw. VDAC2 and the BCL-2 family of proteins. Biochemical Society transactions. 2021 Dec 17;49(6):2787-2795