title: Mitochondrial dynamics in human NADH:ubiquinone oxidoreductase deficiency.
abstract: Mitochondrial NADH:ubiquinone oxidoreductase or complex I (CI) is a frequently affected enzyme in cases of mitochondrial disorders. However, the cytopathological mechanism of the associated pediatric syndromes is poorly understood. Evidence in the literature suggests a connection between mitochondrial metabolism and morphology. Previous quantitative analysis of mitochondrial structure in cultured fibroblasts of 14 patients revealed that mitochondria were fragmented and/or less branched in patients with severe CI deficiency. These patient cells also displayed greatly increased levels of reactive oxygen species (ROS) and marked aberrations in mitochondrial and cellular Ca(2+)/ATP handling upon hormone stimulation. Here, we discuss the interrelationship between these parameters and demonstrate that the hormone-induced increase in mitochondrial Ca(2+) and ATP concentration, as well as the rate of cytosolic Ca(2+) removal, are not related to mitochondrial length and/or degree of branching, but decrease as a function of the number of mitochondria per cell. This suggests that the amount of mitochondria, and not their shape, is important for Ca(2+)-induced stimulation of mitochondrial ATP generation to feed cytosolic ATP-demanding processes.
authors.affiliation: Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Peter H G M
authors.initials: PH
authors.lastname: Willems
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Werner J H
authors.initials: WJ
authors.lastname: Koopman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D042967:Electron Transport Complex I / Q000172:deficiency*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I; D002118:Calcium