Channels voltage-dependent anion

The PBRis distinct from the central BZ receptor although both can be present in the same tissues in differing ratios. PBRs are predominately localized on the outer mitochondrial membrane and are thus intracellular BZ recognition sites. The PBR is composed of three subunits an 18,000 mol wt subunit that binds isoquinoline carboxamide derivatives a 30,000 mol wt subunit that binds BZs and a 32,000 mol wt voltage-dependent anion channel subunit. The porphyrins may be endogenous ligands for the PBR. PBRs are involved in the control of cell proliferation and differentiation and steroidogenesis. 

Joseph-Iiauzun, E., Farges, R., Delmas, P., Ferrara, P. Loison, G. (1997). The Mr 18,000 subunit of the peripheral-type benzodiazepine receptor exhibits both benzodiazepine and isoquinoline carboxamide binding sites in the absence of the voltage-dependent anion channel or of the adenine nucleotide carrier. J. Biol. Chem. 272, 28102-6. 

Several different changes in mitochondria occur during apoptosis. These include a change in membrane potential (usually depolarization), increased production of reactive oxygen species, potassium channel activation, calcium ion uptake, increased membrane permeability and release of cytochrome c and apoptosis inducing factor (AIF) [25]. Increased permeability of the mitochondrial membranes is a pivotal event in apoptosis and appears to result from the formation of pores in the membrane the proteins that form such permeability transition pores (PTP) may include a voltage-dependent anion channel (VDAC), the adenine nucleotide translocator, cyclophilin D, the peripheral benzodiazepine receptor, hexokinase and... 

There are several hypotheses for a specific mechanism by which ONOO- can control the open state of the PTPC. Briefly the PTPC is regulated by primary constituents of the pore, including the inner membrane adenine nucleotide translocase (ANT) and the outer membrane protein voltage-dependent anion channel (VDAC or porin). The VDAC-ANT complex can bind to signaling proteins that modulate permeability transition, such as pro-apoptotic Bax (which opens the pore) and anti-apoptotic Bcl-2... 

Our model of cytochrome c release during apoptosis is not an alternative mechanism to the Bid/Bax-regulated release of cytochrome c. The voltage-dependent anion channel (VDAC) is known to be converted to a cytochrome c-permeant conduit by Bax. Furthermore, Bax protein can... 

McEnery, M.W., Snowman, A.M., Trifiletti, R.R., and Snyder, S.H., 1992, Isolation ofthe mitochondrial benzodiazepine receptor association with the voltage-dependent anion channel and the adenine nucleotide carrier, Proc.Natl.Acad.Sci. U.S.A. 89 3170-3174. 

Crompton, M., Virji, S., and Ward, J. M., 1998, CyclophUin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeabihty transition poie. EurJ Biochem 258 729-735. 

Tsujimoto Y, Shimizu S (2002) The voltage-dependent anion channel an essential player in apoptosis. Biochemie 84 187-193... 

Germain, M., Mathai, J. P., and Shore, G. C., 2002, BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria, J. Biol. Chem. 277, pp. 18053—18060 Gincel, D., Zaid, H., and Shoshan-Barmatz, V., 2001, Calcium binding and translocation by the voltage-dependent anion channel a possible regulatory mechanism in mitochondrial function, Biochem. J. 358, pp. 147-155... 

Vander Heiden, M.G., Li, X. X., Gottlieb, E., Hill, R. B., Thompson, C. B., and Colombini, M., 2001, Bcl-XL promotes the open configuration of die voltage-dependent anion channel and metabolite passage through die outer mitochondrial membrane, J. Biol. Chem. 276, pp. 19414—19419... 

Shoshan-Barmatz V, Gincel D. The voltage-dependent anion channel characterization, modulation, and role in mitochondrial function in cell life and death. Cell Biochem Biophys. 2003 39 279-292. 

UPR VA VDAC VNA WD-40 repeats unfolded protein response viable apoptotic cell voltage-dependent anion channel viable nonapoptotic cell repeated sequence of approximately 40 amino acids, usually tryptophan (W) and aspartate (D) residues... 

Figure 17.3. Permeability transition pore (PTP). The PTP consists of voltage-dependent anion channel (VDAC), adenine nucleotide translocase (ANT) and several associated molecules including cyclophilin D (CypD) and peripheral benzodiazepine receptor (PBR). IMM, inner mitochondrial membrane OMM, outer mitochondrial membrane CytC, cytochrome c.

The mitochondrial permeability transition (MPT) is the loss of the inner mitochondrial membrane impermeability to solutes caused by opening of the MPT pore (MPTP). In turn, this action results in a loss of mitochondrial function and provides a common mechanism implicated in activation of mi-tophagy/autophagy, apoptosis, and necrosis in different cell systems. Although the composition of MPTP is not fully settled, multiple studies suggest involvement of adenine nucleotide translocase (ANT) in the inner mitochondrial membrane, voltage-dependent anion channel (VDAC or porin) in the outer membrane, and cyclophilin D (CypD) in the matrix. 

Yang Z, Schumaker EM, Egorin MJ, Zuhowski EG, Guo Z, 45. Cullen KJ. Cisplatin preferentially binds mitochondrial DNA and voltage-dependent anion channel protein in the mitochondrial membrane of head and neck squamous cell carcinoma possible... 

The outer membrane is quite permeable to most small molecules and ions because it contains many copies of mitochondrialporin, a 30-35 kd poreforming protein also known as VDAC, for voltage-dependent anion channel. 

The molecular structure of the MPT pore is not fully understood either. Current evidence suggests that two proteins, the voltage-dependent anion channel (VDAC), located in the outer mitochondrial membrane, and the adenine nucleotide translocase (ANT-1), located in the inner mitochondrial membrane, combine to form a pore that spans both membranes. 

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