VDAC1
Description
The VDAC1 (voltage dependent anion channel 1) is a protein-coding gene located on chromosome 5.
Voltage-dependent anion-selective channel 1 (VDAC-1) is a beta barrel protein encoded by the VDAC1 gene on chromosome 5. It forms an ion channel in the outer mitochondrial membrane (OMM) and the outer cell membrane. In the OMM, it allows ATP to diffuse out of the mitochondria into the cytoplasm. In the cell membrane, it is involved in volume regulation. Mitochondria are responsible for ATP synthesis and other metabolites needed for cell survival. VDAC1 enables communication between the mitochondrion and the cell, mediating the balance between cell metabolism and cell death. Besides metabolic permeation, VDAC1 also acts as a scaffold for proteins such as hexokinase that can in turn regulate metabolism. This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms (VDAC2 and VDAC3), which are involved in the regulation of cell metabolism, mitochondrial apoptosis, and spermatogenesis. Over expression and misregulation of this pore could lead to apoptosis in the cell leading to a variety of diseases within the body. In particular, since VDAC1 is the major calcium ion transport channel, its dysfunction is implicated in cancer, Parkinson's (PD), and Alzheimer's disease.
VDAC1 forms a channel across the mitochondrial outer membrane and the plasma membrane. In the mitochondria, it allows the passage of small hydrophilic molecules. In the plasma membrane, it contributes to cell volume regulation and apoptosis. VDAC1 adopts an open conformation at low membrane potential and a closed conformation at potentials above 30-40 mV. The open state shows weak anion selectivity, while the closed state is cation-selective. VDAC1 binds to various signaling molecules, including ceramide, phosphatidylcholine, cholesterol, and oxysterol. In depolarized mitochondria, VDAC1 acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis. Polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN reduces mitochondrial calcium influx, inhibiting apoptosis. VDAC1 may participate in the formation of the permeability transition pore complex (PTPC), which releases mitochondrial products that trigger apoptosis. It might also mediate ATP export from cells.
VDAC1 is also known as PORIN, VDAC-1.
Associated Diseases
- cancer
- breast cancer
- acute kidney failure
- diabetes mellitus, transient neonatal, 2
- Pallister-Hall syndrome
