title: Deficiency of the adenine nucleotide translocator in muscle of a patient with myopathy and lactic acidosis: a new mitochondrial defect.
abstract: In a patient with a mitochondrial myopathy, presenting with lactic acidosis, 31P-nuclear magnetic resonance spectroscopy in resting muscle showed half the creatine phosphate level of controls. The creatine phosphate resynthesis rate after aerobic exercise was only 18% of that in controls. However, the activities of complexes I to V catalyzing oxidative phosphorylation and the pyruvate and the 2-oxoglutarate dehydrogenase complexes showed a 2- to 20-fold increase. In line with this, the uncoupled mitochondrial respiration rate was significantly higher than in controls. In contrast, the respiration of the mitochondria from the patient was less stimulated by ADP than that of control mitochondria. This finding could point to a defect in complex V, the enzyme directly involved in ATP synthesis. The activity of complex V, measured as the mitochondrial ATPase activity, and its concentration, as judged from Western blots using antisera against the F1 part of complex V, were, however, also greatly increased in the patient. Alternatively, the transport system, importing ADP into and exporting ATP out of the mitochondrial matrix, the ADP/ATP or adenine nucleotide translocator, could be affected. Immunostaining of Western blots revealed a 4-fold decrease in the concentration of the adenine nucleotide translocator in the patient. Because oxidative phosphorylation was not disturbed in fibroblasts and lymphocytes, we conclude that this patient suffers from a muscle-specific deficiency of his mitochondrial adenine nucleotide translocator, a defect unknown so far.
authors: Het Emma Kinderziekenhuis, Children's Academic Medical Centre, Amsterdam, The Netherlands.
authors: H D
authors: HD
authors: Bakker
authors: H R
authors: HR
authors: Scholte
authors: C
authors: C
authors: Van den Bogert
authors: W
authors: W
authors: Ruitenbeek
authors: J A
authors: JA
authors: Jeneson
authors: R J
authors: RJ
authors: Wanders
authors: N G
authors: NG
authors: Abeling
authors: B
authors: B
authors: Dorland
authors: R C
authors: RC
authors: Sengers
authors: A H
authors: AH
authors: Van Gennip
mesh_terms: D000140:Acidosis, Lactic / Q000150:complications / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002675:Child, Preschool; D004734:Energy Metabolism; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000172:deficiency*; D017240:Mitochondrial Myopathies / Q000150:complications / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010725:Phosphocreatine / Q000378:metabolism
chemical_list: D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases