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Intracellular localization and isoform expression of the voltage-dependent anion channel (VDAC) in normal and dystrophic skeletal muscle

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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.

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Authors and Affiliations

  1. Dipartimento di Neuroscienze, Laboratorio di Medicina Molecolare, Università di Roma Tor Vergata, Roma, Italy

    Roberto Massa, Alessandro Martorana & Loriana Castellani

  2. I.R.C.C.S. Ospedale S. Lucia, Roma, Italy

    Roberto Massa

  3. Dipartimento di Medicina Interna, Laboratorio di Medicina Molecolare, Università di Roma Tor Vergata, Roma, Italy

    Lionel Njl Marlier, Simona Cicconi & Daniela Pierucci

  4. Istituto di Medicina Sperimentale, Consiglio Nazionale delle Ricerche (IMS-CNR), Roma, Italy

    Lionel Njl Marlier & Patrizia Giacomini

  5. Dipartimento di Scienze Chimiche, Laboratorio di Biochimica e Biologia Molecolare, Università di Catania, Catania, Italy

    Vito de Pinto

  6. Sez.B, Tor Vergata, Roma, Italy

    Loriana Castellani

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  1. Roberto Massa
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Massa, R., Marlier, L.N., Martorana, A. et al. Intracellular localization and isoform expression of the voltage-dependent anion channel (VDAC) in normal and dystrophic skeletal muscle. J Muscle Res Cell Motil 21, 433–442 (2000). https://doi.org/10.1023/A:1005688901635

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