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 disturbed 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.
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Abbreviations
- ANT:
-
adenine nucleotide translocator
- CCCP:
-
carbonyl cyanide-p-(trifluoromethoxy)phenylhydrazone
- VDAC:
-
voltage-dependent anion channel
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Acknowledgements
The authors acknowledge U. Stadtmüller, S. Reymann, Prof. Dr. H. Götz (Göttingen, Germany) for helpful discussions and practical cooperation; Dr. G. Brandolin (Grenoble, France) and Dr. H. Bentlage (Nijmegen, The Netherlands) for providing antisera; Dr. M. S. van der Knaap for magnetic resonance imaging studies (Amsterdam, The Netherlands); and Dr. H. Brunner (Nijmegen, The Netherlands) and Prof. F. Palmieri (Bari, Italy) for stimulating discussions.
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Supported by the Prinses Beatrix Fonds Grants 93-018 and 95-0501 (to M.H.) and by Telethon Italy Grant 711 (to V.D.P.). The Department of Pediatrics Nijmegen is participating in the Institute of Fundamental and Clinical Human Movement Sciences (IFKB).
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Huizing, M., Ruitenbeek, W., Thinnes, F. et al. Deficiency of the Voltage-Dependent Anion Channel: A Novel Cause of Mitochondriopathy. Pediatr Res 39, 760–765 (1996). https://doi.org/10.1203/00006450-199605000-00003
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DOI: https://doi.org/10.1203/00006450-199605000-00003
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