title: Intracellular localization and isoform expression of the voltage-dependent anion channel (VDAC) in normal and dystrophic skeletal muscle.
abstract: Voltage-dependent anion channels (VDACs) are a family of pore-forming proteins encoded by different genes, with at least three protein products expressed in mammalian tissues. The major recognized functional role of VDACs is to permit the almost free permeability of the outer mitochondrial membrane (OMM). Although VDAC1 is the best known among VDAC isoforms, its exclusively mitochondrial location is still debated. Therefore, we have measured its co-localization with markers of cellular organelles or compartments in skeletal muscle fibers by single or double immunofluorescence and traditional as well as confocal microscopy. Our results show that VDAC1 immunoreactivity corresponds to mitochondria and sarcoplasmic reticulum, while sarcolemmal reactivity, previously reported, was not observed. Since VDAC1 has been suggested to be involved in the control of oxidative phosphorylation, we sought for possible gene regulation of VDAC1, VDAC2 and VDAC3 in skeletal muscle of the dystrophin-deficient mdx mouse, which suffers of an impaired control of energy metabolism. Our results show that, while VDAC1 mRNA and protein and VDAC2 mRNA are normally expressed. VDAC3 mRNA is markedly down-regulated in mdx mouse muscle at different ages (before, during and after the outburst of myofiber necrosis). This finding suggests a possible involvement of VDAC3 expression in the early pathogenic events of the mdx muscular dystrophy.
authors: Dipartimento di Neuroscienze, Laboratorio di Medicina Molecolare, Università di Roma Tor Vergata, Italy. massa@uniroma2.it
authors: R
authors: R
authors: Massa
authors: L N
authors: LN
authors: Marliera
authors: A
authors: A
authors: Martorana
authors: S
authors: S
authors: Cicconi
authors: D
authors: D
authors: Pierucci
authors: P
authors: P
authors: Giacomini
authors: V
authors: V
authors: De Pinto
authors: L
authors: L
authors: Castellani
mesh_terms: D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics / Q000378:metabolism; D018101:Mice, Inbred mdx / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018272:Porins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D050995:Voltage-Dependent Anion Channel 1; D050996:Voltage-Dependent Anion Channel 2; D050994:Voltage-Dependent Anion Channels
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D018272:Porins; D020033:Protein Isoforms; D012333:RNA, Messenger; 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; D050995:Voltage-Dependent Anion Channel 1