The gene encompasses over 33 kb of DNA; 9 exons.

There are 3 splice variants reported but they all encode the same 282 amino acids protein. One transcript variant has an mRNA product length of 1993 bp (accession number: NM_003374). Processed length 852 bp.

Voltage-dependent anion-selective channel protein 1 (VDAC1, accession number: NP_003365.1) encodes for a protein product length of 283. VDAC1 regulates the flux of mostly anionic metabolites through the outer mitochondrial membrane, which is highly permeable to small molecules. VDAC is the most abundant protein in the outer membrane. Changes in membrane potentials can switch VDAC between open or high-conducting and closed or low-conducting forms.

Mitochondrial porins have been found in all eukaryotic cells studied to date. In mammalian tissues VDAC1 is expressed in many normal and tumour tissues. It has been well characterized in brain, heart, skeletal muscle, and liver. Human cancer cell lines express higher VDAC1 levels than normal cells (Shinohara et al., 2000; Sinamura et al., 2006; Sinamura et al., 2008).

Primarily in the Outer Mitochondrial Membrane (OMM), but in erythrocytes cell death events (eryptosis) it has been found in the plasma membrane (Sridharan et al., 2012).

VDAC1, located at the OMM, is a key protein in regulating the exchange of ions, nucleotides and a variety of metabolites in and out of the mitochondria. As such, VDAC1 serves a crucial role in cellular energy maintenance. It provides a permeation pathway for metabolites and mobile ions between the cytosol and mitochondria. VDACs are also involved in cell death by interacting with apoptotic proteins and releasing apoptotic metabolites to the cytosol.
Protein modifications. VDAC1 has been shown to be phosphorylated in multiple sites: serine, threonine, and tyrosine. Some candidate kinases have been suggested: GSK3, CaM-II, CKI, PKA, PKC, cdc2, p38MAPK, Nek1, EGFR, and SRC. Following reconstitution of VDAC1 into planar lipid bilayers, phosphorylation by PKA reduces the channel current. In rat liver OMM the N-terminal methionine from VDAC1 is removed and the new amino terminal alanine is acetylated. Two separate studies demonstrated that VDAC1 was multiply acetylated in mouse liver, each study reported different sites. VDAC1 is ubiquitinated following mitochondrial depolarization (Narendra et al., 2010).
Protein interactions. Localization of VDAC1 to the OMM makes it a functional anchor point for molecules that interact with the mitochondria. VDAC1 displays binding sites for glycerol kinase, hexokinase (HK), creatine kinase, mitochondrial creatine kinase (MtCK) (interacts with VDAC1 competing with HK and Bax). VDAC also forms complexes with other proteins, such as the ANT, the peripheral benzodiazepine receptor (TSPO), tubulin, the dynein light chain, mtHSP70, the ORDIC channel, glyceraldehyde 3-phosphate dehydrogenase, actin and gelsolin, as well as with apoptosis-regulating proteins, such as members of the Bcl-2 family.
VDAC1 oligomerization. VDAC1 has been shown to assemble into dimers, trimers, tetramers, and higher oligomeric states in a dynamic process, including the VDAC1 purified from liver mitochondria, recombinant human VDAC, and liver or brain mitochondrion-embedded VDAC1. The supramolecular organization of VDAC1 has also been demonstrated using Atomic Force Microscope. Oligomeric assembly of VDAC1 has been shown to be coupled to apoptosis induction, with oligomerization increasing substantially upon apoptosis induction and inhibited by apoptosis blockers.
N-terminal domain. The N-terminus of VDAC1 is 25 amino acids long, and contains an alpha helix (between residues 5-16). In recently published 3-D structures the N-terminus resides within the pore; independent studies show that it could move out of the pore. The N-terminal α-helical segment is proposed to be involved in channel gating, where it could be acting as the voltage sensor and possibly regulating the conductance of ions and metabolites through the VDAC1 pore. VDAC1-N-terminus is required for apoptosis induction, its interaction with HK-I and Bcl2 has a protective effect against apoptosis (Arbel and Shoshan-Barmatz, 2009).

In higher eukaryotes, three VDAC isoforms have been characterized: VDAC1, VDAC2 and VDAC3, encoded by three separate genes. VDACs are highly conserved across species. VDAC1 is the most abundant isoform in most cells, being ten times more prevalent than VDAC2 and 100 times more prevalent than VDAC3 in HeLa cells (De Pinto et al., 2010). Recently it was demonstrated that while VDAC1 and VDAC2 are localized mainly within the same distinct domains of the OMM, VDAC3 is mostly distributed uniformly over the surface of the mitochondrion.

Direct DNA sequencing of colorectal cancer (CRC) and gastric cancer (GC) led to identification of a recurrent VDAC1 mutation. This mutation, c.332delA, leads to a premature stop codon, resulting in truncation of the amino acid synthesis (p.Asn111MetfsX34) and would remove about 60% length of C-terminal VDAC1 protein. The DNA sequencing indicated that the mutation was heterozygous. There was no significant difference of the mutations with respect to the clinicopathologic features of the GC and CRC (Fishers exact test, p>0,05) (Yoo et al., 2011).