title: Deficiency of the voltage-dependent anion channel: a novel cause of mitochondriopathy.
abstract: A patient with a deficient voltage-dependent anion channel (VDAC) is reported, presenting clinically with psychomotor retardation and minor dysmorphic features. Biochemical studies on muscle mitochondria showed impaired rates of pyruvate oxidation and ATP production; however, no specific deficient activity of one of the mitochondrial enzymes was involved. Western blotting experiments indicated an almost complete VDAC deficiency in skeletal muscle. The only moderately decreased VDAC content in the patient's fibroblasts might indicate that VDAC is expressed in a tissue-specific manner. The deficiency is likely caused by a mutation in the HVDAC1 gene or by a distributed posttranslational modification. This is the first described deficiency of a component of the outer mitochondrial membrane associated with the pyruvate oxidation pathway. Defects in this membrane should be considered as a possible cause of otherwise unexplained mitochondrial disorders.
authors.affiliation: Department of Pediatrics, University Hospital, Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Huizing
authors.forename: W
authors.initials: W
authors.lastname: Ruitenbeek
authors.forename: F P
authors.initials: FP
authors.lastname: Thinnes
authors.forename: V
authors.initials: V
authors.lastname: DePinto
authors.forename: U
authors.initials: U
authors.lastname: Wendel
authors.forename: F J
authors.initials: FJ
authors.lastname: Trijbels
authors.forename: L M
authors.initials: LM
authors.lastname: Smit
authors.forename: H J
authors.initials: HJ
authors.lastname: ter Laak
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
mesh_terms: D002675:Child, Preschool; D006801:Humans; D007473:Ion Channels / Q000172:deficiency* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism*; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018272:Porins; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D050995:Voltage-Dependent Anion Channel 1; D050994:Voltage-Dependent Anion Channels
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; D018272:Porins; D011773:Pyruvates; C494762:VDAC1 protein, human; D050994:Voltage-Dependent Anion Channels; D019289:Pyruvic Acid; D050995:Voltage-Dependent Anion Channel 1