Document 0503
 DOCN  M9590503
 TI    Subcellular localization of human voltage-dependent anion channel
       isoforms.
 DT    9509
 AU    Yu WH; Wolfgang W; Forte M; Vollum Institute for Advanced Biomedical
       Research, Portland,; Oregon, USA.
 SO    J Biol Chem. 1995 Jun 9;270(23):13998-4006. Unique Identifier : AIDSLINE
       MED/95294003
 AB    The voltage-dependent anion channel of the outer mitochondrial membrane,
       VDAC (also known as mitochondrial porin), is a small abundant protein
       which forms a voltage-gated pore when incorporated into planar lipid
       bilayers. This protein forms the primary pathway for movement of major
       metabolites through the outer membrane. Recently, it has been
       demonstrated that two human VDAC genes, HVDAC1 and HVDAC2, produce three
       proteins that differ most significantly at their amino termini. These
       results suggest that the distinct amino termini lead to the targeting of
       individual VDAC isoforms to different cellular compartments. Consistent
       with this hypothesis, recent reports suggest that HIV-DAC1 is found in
       the plasma membrane of mammalian cells. To define the subcellular
       location of HVDAC isoforms, HVDAC genes were modified so that the
       encoded proteins contain COOH-terminal epitopes recognized by either of
       two monoclonal antibodies. Introduction of these epitope tags had no
       effect on the function of modified VDAC proteins. Epitope-tagged
       proteins were then individually expressed in COS7 cells or rat
       astrocytes and the intracellular location of each isoform subsequently
       identified by subcellular fractionation, light level immunofluorescence,
       and immunoelectron microscopy. Our results demonstrate that each HVDAC
       protein is exclusively located in fractions or subcellular regions
       containing mitochondrial marker proteins. In addition,
       immunofluorescence and immunoelectron microscopy show that an individual
       mitochondrion can contain both HVDAC1 and HVDAC2. Our results call into
       question previous reports demonstrating VDAC molecules in the plasma
       membrane and suggest that functional differences between individual VDAC
       isoforms may result in distinct regulatory processes within a single
       mitochondrion.
 DE    Amino Acid Sequence  Animal  Human  *Ion Channels  Membrane
       Proteins/*ANALYSIS/BIOSYNTHESIS/CHEMISTRY  Mice  Microscopy,
       Immunoelectron  Molecular Sequence Data  Rats  Support, U.S. Gov't,
       P.H.S.  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).