Disease relevance of POR1

• Several forms of the voltage-dependent anion-selective channel (VDAC) have been expressed at high yield in Escherichia coli [1].
• We report that por1-Delta strains lacking the mitochondrial porin, Por1p, but not por2-Delta strains lacking the related porin, share some phenotypes similar to the cyc2-Delta2 strain, including hypersensitivity to KCl in glycerol medium [2].

High impact information on POR1

• In contrast, a respiratory-competent strain that lacked the outer mitochondrial membrane Por1 protein showed increased sensitivity to Bax expression [3].
• BAX-induced growth arrest was independent of the tested mitochondrial components, including voltage-dependent anion channel (VDAC), the catalytic beta subunit or the delta subunit of the F(0)F(1)-ATP synthase, mitochondrial cyclophilin, cytochrome c, and proteins encoded by the mitochondrial genome as revealed by [rho(0)] cells [4].
• However, cells missing the POR1 gene (delta por1) were able to grow on yeast media containing a nonfermentable carbon source (glycerol) but not on such media at elevated temperature (37 degrees C) [5].
• Multicopy suppressors of phenotypes resulting from the absence of yeast VDAC encode a VDAC-like protein [5].
• These results rule out the contention that VDAC is indispensable for establishing the benzodiazepine binding site and are in agreement with the hypothesis that the Mr 18,000 subunit carries both the isoquinoline carboxamide and benzodiazepine binding domains [6].

Biological context of POR1

• Two of them, namely the TOM complex channel (translocase of the outer membrane) and the PSC (peptide-sensitive channel) participate in protein translocation and are probably identical, whereas a channel-forming protein called VDAC (voltage-dependent anion channel) serves as the major pathway for metabolites [7].
• Processes underlying the upregulation of Tom proteins in S. cerevisiae mitochondria depleted of the VDAC channel [8].
• To clarify the role of VDAC and of the adenine nucleotide carrier, if any, in the constitution of the benzodiazepine binding site, yeast host strains were constructed in which the corresponding genes had been knocked out [6].
• This ability of NADH to facilitate VDAC closure could be one mechanism by which glycolysis can suppress oxidative phosphorylation (Crabtree effect) [9].
• Large scale rearrangement of protein domains is associated with voltage gating of the VDAC channel [10].

Anatomical context of POR1

• The permeability of the outer mitochondrial membrane to most metabolites is believed to be based in an outer membrane, channel-forming protein known as VDAC (voltage-dependent anion channel) [5].
• The presented data indicate that in S. cerevisiae-uncoupled mitochondria, external NADH, applied at higher concentrations (above 50 nmoles per 0.1 mg of mitochondrial protein), may use the TOM complex channel, besides VDAC1, to cross the outer membrane [7].
• The VDAC channel of the mitochondrial outer membrane is voltage-gated like the larger, more complex voltage-gated channels of the plasma membrane [10].
• Labeling of amoeba, yeast and rat liver mitochondria with [(3)H]Ro5-4864 revealed proteins identified as the voltage dependent anion selective channel (VDAC) in the outer membrane and adenine nucleotide translocase (ANT) in the inner membrane [11].
• When VDAC is reconstituted into phospholipid (soybean) membranes, the two gating processes have virtually the same steepness of voltage dependence and the same midpoint voltage [12].

Associations of POR1 with chemical compounds

• This protein has been found to copurify with two other mitochondrial proteins, namely the outer membrane voltage-dependent anion channel (VDAC), also known as mitochondrial porin, and the inner membrane adenine nucleotide carrier [6].
• Its effects, different from the reported functional interactions of the channel with hexo- or creatine kinases, could not be mimicked by the protein termed VDAC modulator, indicating the presence of a novel VDAC modulator [13].
• We find that one substitution mutation (lys 61 to glu) alters the selectivity of VDAC [14].
• Previous in vitro studies indicated that mutation of both K234 and K236 to arginine, glutamine, or glutamic acid impaired the ability of the voltage-dependent anion channel (VDAC1) to insert into the outer membrane of the mitochondria (Smith et al. 1995) [15].
• In addition, we have shown that the purified protein, when reconstituted into liposomes, can bind hexokinase in a glucose-6-phosphate dependent manner, as has been shown for VDAC purified from other sources [16].

Physical interactions of POR1

• Biochemically, SFK1 interacts with Por1p, a channel protein in the outer mitochondrial membrane, suggesting that SFK1 interacts with the mitochondria directly [17].

Regulatory relationships of POR1

• Consequently, it may be concluded that depletion of the VDAC channel might influence differentially the expression of TOM40 and TOM70 genes [8].

Other interactions of POR1

• In addition to the POR1 gene, which encodes the well-characterized voltage dependent anion-selective channel (YVDAC1) of the mitochondrial outer membrane, the yeast Saccharomyces cerevisiae contains a second gene (POR2) encoding a protein (YVDAC2) with 50% sequence identity to YVDAC1 [18].
• Requirements of Cyc2p and the porin, Por1p, for ionic stability and mitochondrial integrity in Saccharomyces cerevisiae [2].

Analytical, diagnostic and therapeutic context of POR1

• The gene encoding the yeast mitochondrial outer membrane channel VDAC was subjected to site-directed mutagenesis to change amino acids at 29 positions to residues differing in charge from the wild-type sequence [19].
• Molecular genetics of the VDAC ion channel: structural model and sequence analysis [20].
• Direct measurement of VDAC-actin interaction by surface plasmon resonance [21].

References