VDAC1

This gene encodes a voltage-dependent anion channel protein that is a major component of the outer mitochondrial membrane. The encoded protein facilitates the exchange of metabolites and ions across the outer mitochondrial membrane and may regulate mitochondrial functions. This protein also forms channels in the plasma membrane and may be involved in transmembrane electron transport. Alternate splicing results in multiple transcript variants. Multiple pseudogenes of this gene are found on chromosomes 1, 2 3, 6, 9, 12, X and Y.

voltage dependent anion channel 1

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 (PubMed:11845315, PubMed:18755977, PubMed:20230784, PubMed:8420959).
Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol (PubMed:31015432).
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 (PubMed:32047033).
May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756).
May mediate ATP export from cells (PubMed:30061676).

Biological Process anion transport Source:UniProtKB1 Publication
Biological Process apoptotic process Source:UniProtKB1 Publication
Biological Process behavioral fear response Source:Ensembl
Biological Process epithelial cell differentiation Source:UniProtKB1 Publication
Biological Process learning Source:Ensembl
Biological Process negative regulation of apoptotic process Source:UniProtKB1 Publication
Biological Process negative regulation of calcium import into the mitochondrion Source:UniProtKB1 Publication
Biological Process negative regulation of reactive oxygen species metabolic process Source:Ensembl
Biological Process neuron-neuron synaptic transmission Source:Ensembl
Biological Process positive regulation of parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization Source:UniProtKB1 Publication
Biological Process pyruvate metabolic process Source:Reactome
Biological Process regulation of autophagy of mitochondrion Source:ParkinsonsUK-UCL1 Publication

Mitochondrion outer membrane
Cell membrane
Membrane raft

Phosphorylation at Ser-193 by NEK1 promotes the open conformational state preventing excessive mitochondrial membrane permeability and subsequent apoptotic cell death after injury. Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably by preventing ubiquitin-mediated proteasomal degradation.
Ubiquitinated (PubMed:25621951, PubMed:32047033).
Undergoes monoubiquitination and polyubiquitination by PRKN; monoubiquitination at Lys-274 inhibits apoptosis, whereas polyubiquitination leads to its degradation and promotes mitophagy (PubMed:25621951, PubMed:32047033).
Deubiquitinated by USP30 (PubMed:25621951).