Fig. 6: Summary of possible models for voltage-dependent anion channel 2 (VDAC2) regulation of Bid. | Cell Death & Disease

Fig. 6: Summary of possible models for voltage-dependent anion channel 2 (VDAC2) regulation of Bid.

From: BioID-based proteomic analysis of the Bid interactome identifies novel proteins involved in cell-cycle-dependent apoptotic priming

Fig. 6

A Caspase-8-cleaved Bid or exogenously expressed tBid acts as a direct activator BH3-only protein. VDAC2 has been shown to interact with Bak and Bax at mitochondria, and this interaction is necessary for their recruitment to the OMM35,42. Activation of Bid by caspase 8 then allows tBid to activate mitochondrial bound Bak, resulting in apoptosis commitment and MOMP. In an alternative model, VDAC2 suppresses Bak activation until it is displaced by direct activator BH3 proteins such as tBid34. B In mitosis, FL-Bid acts as a sensitiser BH3-only protein, shifting apoptotic priming but not driving commitment to MOMP. Phosphorylation of FL-Bid at serine 66 allows its recruitment proximal to VDAC2 and increases priming, but commitment only results if mitotic exit is delayed. Possible mechanisms by which pS66 Bid mediates an increase in priming are through direct interaction with VDAC2, or by interacting with VDAC2-bound proteins, such as Bak. Upon transition to anaphase, Bid is dephosphorylated and priming is reduced.

Back to article page