Disease relevance of Vdac1

• CONCLUSIONS: These results suggest that VDAC is involved in PTP activity and/or regulation and thus is an important player in retinal degeneration associated with PTP-mediated mitochondrial dysfunction [1].
• VDAC was present in mitochondria of all retinal cell types: photoreceptor, bipolar, horizontal, amacrine, and ganglion cells [1].
• Hexokinase receptor complex in hepatoma mitochondria: evidence from N,N'-dicyclohexylcarbodiimide-labeling studies for the involvement of the pore-forming protein VDAC [2].

High impact information on Vdac1

• We therefore propose that Akt increases coupling of glucose metabolism to oxidative phosphorylation and regulates PT pore opening via the promotion of hexokinase-VDAC interaction at the outer mitochondrial membrane [3].
• Hexokinases are known to bind to VDAC and directly couple intramitochondrial ATP synthesis to glucose metabolism [3].
• Activated Akt, like Bcl-2 and Bcl-xL, prevents closure of a PT pore component, the voltage-dependent anion channel (VDAC); intracellular acidification; mitochondrial hyperpolarization; and the decline in oxidative phosphorylation that precedes cytochrome c release [3].
• Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria [4].
• As to the functional consequences, VDAC-overexpressing cells are more susceptible to ceramide-induced cell death, thus confirming that mitochondrial Ca2+ uptake plays a key role in the process of apoptosis [4].

Biological context of Vdac1

• This indicates that the increase in the pore size of VDAC after its interaction with Bax and tBid is controlled via phosphorylation of this channel by PKA [5].
• Voltage-dependent anion channel (VDAC), Bax, and tBid play a central role in apoptosis regulation but their functioning is still very controversial [6].
• By its kinetics, its selectivity and its potential-dependence, this channel differs from the voltage-dependent anion channel of outer mitochondrial membranes [7].
• In the forebrain of control rats, hippocampal voltage-dependent anion channel and adenine nucleotide carrier abundance was relatively low, while isoquinoline binding protein abundance did not differ between hippocampus and the rest of the forebrain [8].
• In this paper we demonstrate that VDAC purified from rat liver mitochondria can be phosphorylated by the catalytic subunit of cAMP dependent protein kinase (PKA) [9].

Anatomical context of Vdac1

• VDAC forms voltage gated pore in planar lipid bilayers, and acts as the pathway for the movement of substances in and out of the mitochondria by passive diffusion [6].
• These results reveal a novel function for the widely expressed VDAC channel, identifying it as a molecular component of the routes for Ca2+ transport across the mitochondrial membranes [4].
• The beta(2) and beta(3) subunits of the GABA(A) receptor were co-immunoprecipitated by the VDAC-1 antibody suggesting a physical association between VDAC-1 and GABA(A) receptors in rat brain membranes [10].
• Bax interacts with the voltage-dependent anion channel and mediates ethanol-induced apoptosis in rat hepatocytes [11].
• Polyclonal antiserum to a new voltage-dependent anion channel protein (B-36 VDAC) isolated during the purification of the GABAA receptor from bovine cerebral cortex was used to determine the localization of this protein in immunocytochemical preparations of cerebral cortex, cerebellum and hippocampal formation of rat, cow and human [12].

Associations of Vdac1 with chemical compounds

• Photoaffinity labeling with a neuroactive steroid analogue. 6-azi-pregnanolone labels voltage-dependent anion channel-1 in rat brain [10].
• RESULTS: Retinal VDACs exhibited the electrophysiological fingerprint of the VDAC superfamily [1].
• The intra-mitochondrial cytochrome c distribution varies correlated to the formation of a complex between VDAC and the adenine nucleotide translocase: this affects Bax-dependent cytochrome c release [13].
• (v) Hexokinase was furthermore used as a tool to isolate the contact site forming complex of outer membrane VDAC and inner membrane ANT from Triton-dissolved membranes [13].
• The mitochrondrial benzodiazepine receptor (mBzR) binds a subset of benzodiazepines and isoquinoline carboxamides with nanomolar affinity and consists of the voltage-dependent anion channel, the adenine nucleotide translocator, and an 18-kDa protein [14].

Other interactions of Vdac1

• Most cells primarily expressed VDAC-1, but they also expressed VDAC-2 and -3 [1].
• We further established for the first time that the C-terminal domain of Mcl-1 became proapoptotic as a result of caspase-3 cleavage, and its physical interaction and cooperation with tBid, Bak, and voltage-dependent anion-selective channel 1 promoted mitochondrial apoptosis [15].
• (iii) The outer membrane pore (VDAC) acquires high capacity for hexokinase binding by interacting with the ANT [13].
• Peripheral-type benzodiazepine receptors (PBR) are constituted by three protein components, the isoquinoline binding protein (IBP), the voltage-dependent anion channel (VDAC), and the adenine nucleotide transporter (ANT) [16].
• A pronounced depletion in the content of the adenine nucleotide translocator (ANT) was observed by Western blotting, while no alterations were found in the mitochondrial voltage-dependent anion channel content [17].

Analytical, diagnostic and therapeutic context of Vdac1

• Relative levels of the mRNAs coding the VDAC isoforms in rat, rabbit, and bovine brain were determined by RT-PCR [18].
• Prevention of Bax-VDAC interactions by a microinjection of anti-VDAC antibody effectively prevented hepatocyte apoptosis by ethanol [11].
• The 32-kDa band on SDS/PAGE resolved into a doublet and reacted with antibodies against the voltage-dependent anion channel (porin) and the adenine nucleotide translocase [19].
• 1. Properties of the voltage-dependent anion-selective channel in cultured smooth muscle cells of the rat aorta were studied using the patch-clamp technique [20].
• In the present study, changes in membrane status were examined by immuno-electron microscopy using antibodies against the voltage-dependent anion channel (VDAC), beta-subunit of F1-ATPase (F1beta), and cytochrome c (cyt. c) [21].

References