- Peptide (C)DGKNVNAGGHK, corresponding to amino acid residues of 264-274 of rat VDAC1 (Accession Q9Z2L0). Intracellular.
- Western blot analysis of rat kidney (lanes 1 and 4), rat brain (lanes 2 and 5), mouse brain (lanes 3 and 6) membranes and CCF-SSTGI (lanes 7 and 8) cell line lysate:1-3,7. Anti-VDAC Antibody (#AVC-001), (1:200).
4-6,8. Anti-VDAC Antibody, preincubated with Pan VDAC Blocking Peptide (#BLP-VC001).
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The voltage-dependent anion channel (VDAC) is an outer mitochondrial membrane channel protein. It is required for proper mitochondrial function and as such is ubiquitously expressed. The three isoforms expressed in higher eukaryotes are highly conserved. VDAC1, VDAC2 and VDAC3 allow the movement of most metabolites in and out of the mitochondria. The channel spans the membrane 19 times through antiparallel β strands1-3.
Studies show that VDAC channels exhibit ion selectivity and are voltage-dependent. When in the open state, VDAC channels conduct mainly organic anions such as ATP, ADP and inorganic phosphate (Pi). In the closed state they still conduct ions, but much smaller and mostly inorganic, such as K+, Na+ and Ca2+ 4-5. While cells are metabolically active, VDAC channels are constitutively open in order to enable oxidative phosphorylation in the mitochondria to take place (through the passage of ADP across the membrane)4.
VDAC channels are best described for their role in apoptosis. In the early stages of the signaling pathway, a proapoptotic factor, a member of the Bcl2 family, is responsible for closing the channel thereby decreasing the release of ADP and ATP from the mitochondria4.
VDAC channels are also implicated in the Warburg effect, which is typical of cancer cells. In such cells, hexokinase (the first enzyme in the glycolytic pathway responsible for phosphorylating glucose on C6 to yield glucose-6 phosphate) known to be up-regulated, binds to VDAC1 and takes up most of the ATP released by the channel in order to phosphorylate glucose. This action speeds up glycolysis if downstream reactions function properly. If however a glycolysis step is inhibited or down-regulated, glucose-6-phosphate builds up and consequently inhibits hexokinase, thereby restoring proper mitochondrial function4.
VDAC is also detected in the plasma membrane of various cell types including lymphocytes, epithelial cells, and astrocytes6. The postulated roles for VDAC in the plasma membrane mainly involve the regulation of cellular ATP release and volume control7. VDACs have also been proposed to function as the plasma membrane maxi anion channels8.
None of the isoforms are essential for viability. Knock-out of VDAC3 in mice causes sterility in males9. That of VDAC1 and VDAC2 affects breathing10 and the individual knock-out of VDAC1 causes embryonic death in mice in some cases11.
Species reactivity key:
Alomone Labs is pleased to offer a highly specific antibody directed against an epitope of rat VDAC1. Anti-VDAC Antibody (#AVC-001) can be used in western blot analysis. It is a pan antibody recognizing VDAC1, VDAC2 and VDAC3 from human, rat and mouse samples.
- Mouse gastrocnemius muscle lysate (1:1000).
Bal, N.C. et al. (2016) J. Biol. Chem. 291, 17247.