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

Voltage-dependent anion channels (VDACs) are a family of pore-forming proteins encoded by di erent genes, withat least three protein products expressed in mammalian tissues. The major recognized functional role of VDACs is topermit the almost free permeability of the outer mitochondrial membrane (OMM). Although VDAC1 is the bestknown among VDAC isoforms, its exclusively mitochondrial location is still debated. Therefore, we have measuredits co-localization with markers of cellular organelles or compartments in skeletal muscle ®bers by single or doubleimmuno¯uorescence and traditional as well as confocal microscopy. Our results show that VDAC1 immunore-activity 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, wesought for possible gene regulation of VDAC1, VDAC2 and VDAC3 in skeletal muscle of the dystrophin-de®cientmdx mouse, which su ers of an impaired control of energy metabolism. Our results show that, while VDAC1mRNA and protein and VDAC2 mRNA are normally expressed, VDAC3 mRNA is markedly down-regulated inmdx mouse muscle at di erent ages (before, during and after the outburst of myo®ber necrosis). This ®ndingsuggests a possible involvement of VDAC3 expression in the early pathogenic events of the mdx muscular dystrophy.