Voltage-dependent anion-selective channel protein 1

Definition:

Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol. In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis. May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis. May mediate ATP export from cells.

References:

[1]. Shashank Dadsena, et al. Ceramides bind VDAC2 to trigger mitochondrial apoptosis. Nat Commun. 2019 Apr 23;10(1):1832. [Content Brief]

[2]. Florence Verrier, et al. Study of PTPC composition during apoptosis for identification of viral protein target. Ann N Y Acad Sci. 2003 Dec;1010:126-42. [Content Brief]

[3]. Su Jin Ham, et al. Decision between mitophagy and apoptosis by Parkin via VDAC1 ubiquitination. Proc Natl Acad Sci U S A. 2020 Feb 25;117(8):4281-4291. [Content Brief]

[4]. Sebastian Hiller, et al. Solution structure of the integral human membrane protein VDAC-1 in detergent micelles. Science. 2008 Aug 29;321(5893):1206-10. [Content Brief]

[5]. Yumay Chen, et al. Phosphorylation by Nek1 regulates opening and closing of voltage dependent anion channel 1. Biochem Biophys Res Commun. 2010 Apr 9;394(3):798-803. [Content Brief]

[6]. Irene Marginedas-Freixa, et al. Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1. Sci Rep. 2018 Jul 30;8(1):11384. [Content Brief]

[7]. F P Thinnes, et al. Gadolinium as an opener of the outwardly rectifying Cl(-) channel (ORCC). Is there relevance for cystic fibrosis therapy?. Pflugers Arch. 2001;443 Suppl 1:S111-6. [Content Brief]

[8]. Lei Li, et al. Plasminogen kringle 5 induces endothelial cell apoptosis by triggering a voltage-dependent anion channel 1 (VDAC1) positive feedback loop. J Biol Chem. 2014 Nov 21;289(47):32628-38. [Content Brief]

[9]. E Blachly-Dyson, et al. 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. [Content Brief]

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