Is there VDAC in cell compartments other than the mitochondria?
ABSTRACT Higher eukaryotes, including mammals and plants, express a family of VDAC proteins each encoded by a distinct gene. Two human genes encoding VDAC isoforms (HVDAC1 and HVDAC2) have been characterized in greatest detail. These genes generate three proteins that differ primarily by the addition of distinct N terminal extensions in HVDAC2 and HVDAC2', a splice variant of HVDAC2, relative to HVDAC1. Since N terminal sequences have been demonstrated to target many proteins to appropriate subcellular compartments, this observation raises the possibility that the N terminal differences found in HVDAC isoforms may lead to targeting of each protein to different cellular locations. Consistent with this hypothesis, a large number of reports have provided evidence consistent with the notion that HVDAC1 and its homolog in related mammalian species may specifically be present in the plasma membrane or other nonmitochondrial cellular compartments. Here, we review this information and conclude that if VDAC molecules are present at nonmitochondrial locations in mammalian cells, these are unlikely to be the known products of the HVDAC1 or HVDAC2 genes.
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ABSTRACT: Background/Aims: Voltage-dependent anion channels (VDAC), also known as eukaryotic porins, are located in the outer mitochondrial membrane and allow the flux of ions and small metabolites. While the pore-forming ability of recombinant VDAC1 and VDAC2 has been extensively studied during the last decades, a clear-cut ion conducting channel activity has not been assigned to the VDAC3 isoform. Methods : Electrophysiological characterization of the recombinant protein purified and refolded was obtained after incorporation into planar lipid bilayers. Results: Here we report for the first time that recombinant hVDAC3, upon expression in E.coli and purification-refolding, shows a channel activity with a very small conductance (90 pS in 1 M KCl) with respect to the conductance of hVDAC1 (>3500 pS in 1 M KCl). Purified hVDAC3 allowed the passage of both chloride and gluconate anions and did not distinguish between potassium, sodium and calcium used as cations. In contrast to VDAC1, the channel was active also at transmembrane voltages higher than +/-40 mV and displayed a relatively high open probability even at +/-80 mV. hVDAC3 was only slightly voltage-dependent, displaying a tendency to adopt lower-conductance states at positive voltages applied to the cis chamber. In accordance with the small conductance of the pore, expression of hVDAC3 in a porin-less yeast strain allowed only partial recovery of the growth under non-permissive conditions. Conclusion: The observed electrophysiological properties of hVDAC3 are surprisingly different from the other isoforms and are discussed in relation to the proposed physiological role of the protein in mammalian cells. © 2014 S. Karger AG, Basel.Cellular Physiology and Biochemistry 08/2014; 34(3):842-853. DOI:10.1159/000363047 · 3.55 Impact Factor
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ABSTRACT: The field of mitochondrial ion channels has recently seen substantial progress, including the molecular identification of some of the channels. An integrative approach using genetics, electrophysiology, pharmacology, and cell biology to clarify the roles of these channels has thus become possible. It is by now clear that many of these channels are important for energy supply by the mitochondria and have a major impact on the fate of the entire cell as well. The purpose of this review is to provide an up-to-date overview of the electrophysiological properties, molecular identity, and pathophysiological functions of the mitochondrial ion channels studied so far and to highlight possible therapeutic perspectives based on current information.Physiological Reviews 04/2014; 94(2):519-608. DOI:10.1152/physrev.00021.2013 · 29.04 Impact Factor
Journal of Biological Chemistry 04/2012; 287(15):12156-12156. DOI:10.1074/jbc.N111.314229 · 4.60 Impact Factor