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Structural highlights

Function

VDAC2_HUMAN Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:8420959). The channel adopts an open conformation at zero mV and a closed conformation at both positive and negative potentials (PubMed:8420959). There are two populations of channels; the main that functions in a lower open-state conductance with lower ion selectivity, that switch, in a voltage-dependent manner, from the open to a low-conducting 'closed' state and the other that has a normal ion selectivity in the typical high conductance, 'open' state (PubMed:8420959). Binds various lipids, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:31015432). Binding of ceramide promotes the mitochondrial outer membrane permeabilization (MOMP) apoptotic pathway (PubMed:31015432).^{[1] [2]} Catalyzes the scrambling of phospholipids across the outer mitochondrial membrane; the mechanism is unrelated to channel activity and is capable of translocating both anionic and zwitterionic phospholipids.^[3]

References

1. ↑ Dadsena S, Bockelmann S, Mina JGM, Hassan DG, Korneev S, Razzera G, Jahn H, Niekamp P, Müller D, Schneider M, Tafesse FG, Marrink SJ, Melo MN, Holthuis JCM. Ceramides bind VDAC2 to trigger mitochondrial apoptosis. Nat Commun. 2019 Apr 23;10(1):1832. PMID:31015432 doi:10.1038/s41467-019-09654-4
2. ↑ Blachly-Dyson E, Zambronicz EB, Yu WH, Adams V, McCabe ER, Adelman J, Colombini M, Forte M. Cloning and functional expression in yeast of two human isoforms of the outer mitochondrial membrane channel, the voltage-dependent anion channel. J Biol Chem. 1993 Jan 25;268(3):1835-41 PMID:8420959
3. ↑ Jahn H, Bartoš L, Dearden GI, Dittman JS, Holthuis JCM, Vácha R, Menon AK. Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase. Nat Commun. 2023 Dec 8;14(1):8115. PMID:38065946 doi:10.1038/s41467-023-43570-y