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Voltage-Dependent Anion Channel (VDAC)

VDAC inhibitors act on voltage-dependent anion channels (VDAC), pores in the outer mitochondrial membrane. Three isoforms, VDAC1, VDAC2 and VDAC3, let ATP, ADP, metabolites and ions pass between the cytosol and mitochondria. VDAC1 also binds hexokinase and proteins of the B-cell lymphoma 2 (Bcl-2) family, which links the channel to apoptosis. In 2007, the small molecule erastin was found to cause oxidative cell death through VDAC2 and VDAC3, a process later named ferroptosis. VBIT-4 and VBIT-12 inhibit VDAC1, while WEHI-9625 and DIDS sodium salt are further channel inhibitors. The set is mixed: RSL3 targets glutathione peroxidase 4 (GPX4), and HK2-IN-4 inhibits hexokinase 2.

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