title: Primary fibroblasts of NDUFS4(-/-) mice display increased ROS levels and aberrant mitochondrial morphology.
abstract: The human NDUFS4 gene encodes an accessory subunit of the first mitochondrial oxidative phosphorylation complex (CI) and, when mutated, is associated with progressive neurological disorders. Here we analyzed primary muscle and skin fibroblasts from NDUFS4(-/-) mice with respect to reactive oxygen species (ROS) levels and mitochondrial morphology. NDUFS4(-/-) fibroblasts displayed an inactive CI subcomplex on native gels but proliferated normally and showed no obvious signs of apoptosis. Oxidation of the ROS sensor hydroethidium was increased and mitochondria were less branched and/or shorter in NDUFS4(-/-) fibroblasts. We discuss the relevance of these findings with respect to previous results and therapy development.
authors.affiliation: Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Federica
authors.initials: F
authors.lastname: Valsecchi
authors.forename: Sander
authors.initials: S
authors.lastname: Grefte
authors.forename: Peggy
authors.initials: P
authors.lastname: Roestenberg
authors.forename: Jori
authors.initials: J
authors.lastname: Joosten-Wagenaars
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Peter H G M
authors.initials: PH
authors.lastname: Willems
authors.forename: Werner J H
authors.initials: WJ
authors.lastname: Koopman
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D042967:Electron Transport Complex I / Q000172:deficiency*; D005347:Fibroblasts / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: C534449:Ndufs4 protein, mouse; D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I