VDAC1 as Janus in cell death and survival: Annexin A5 to the rescue

Abstract

VDAC1, a large conductance channel in the outer mitochondrial membrane, plays a crucial role in mitochondrial physiology. VDAC1 supports cellular metabolism and survival by serving as a mitochondrial Ca²⁺-uptake and ATP-exit system. Conversely, VDAC1 also contributes to apoptosis by forming oligomeric pores mediating cytochrome c release. Recently, Oflaz et al., EMBO J, 2025, identified the Ca²⁺-binding protein Annexin A5 as a dynamic, Ca²⁺-dependent switch that enhances VDAC1’s Ca²⁺-transport function while at the same time preventing pro-apoptotic VDAC1 oligomer formation.