The murine voltage-dependent anion channel gene family. Conserved structure and function.
Voltage-dependent anion channels (VDACs) are pore-forming proteins found in the outer mitochondrial membrane of all eucaryotes. VDACs are the binding sites for several cytosolic enzymes, including the isoforms of hexokinase and glycerol kinase. VDACs have recently been shown to conduct ATP when in the open state, allowing bound kinases preferential access to mitochondrial ATP and providing a possible mechanism for the regulation of adenine nucleotide flux. Two human VDAC cDNAs have been described previously, and we recently reported the isolation of mouse VDAC1 and VDAC2 cDNAs, as well as a third novel VDAC cDNA, designated VDAC3. In this report we describe the structural organization of each mouse VDAC gene and demonstrate that, based on conserved exon/intron boundaries, the three VDAC isoforms belong to a single gene family. The 5'-flanking region of each VDAC gene was shown to have transcription promoter activity by transient expression in cultured cells. The promoter region of each VDAC isoform lacks a canonical TATA box, but all are G+C-rich, a characteristic of housekeeping gene promoters. To examine the conservation of VDAC function, each mouse VDAC was expressed in yeast lacking the endogenous VDAC gene. Both VDAC1 and VDAC2 are able to complement the phenotypic defect associated with the mutant yeast strain. VDAC3, however, is only able to partially complement the mutant phenotype, suggesting an alternative physiologic function for the VDAC3 protein.
Sampson
M J
MJ
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Lovell
R S
RS
Craigen
W J
WJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010957:Plasmids / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D018272:Porins; D011401:Promoter Regions, Genetic; D017433:Protein Structure, Secondary; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D050995:Voltage-Dependent Anion Channel 1; D050996:Voltage-Dependent Anion Channel 2; D050994:Voltage-Dependent Anion Channels
D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018272:Porins; C494762:VDAC1 protein, human; C494765:VDAC2 protein, human; C494768:VDAC3 protein, human; C494763:Vdac1 protein, mouse; C494766:Vdac2 protein, mouse; D050996:Voltage-Dependent Anion Channel 2; D050994:Voltage-Dependent Anion Channels; D011061:Poly A; D050995:Voltage-Dependent Anion Channel 1