Primary fibroblasts of NDUFS4(-/-) mice display increased ROS levels and aberrant mitochondrial morphology

Mitochondrion. 2013 Sep;13(5):436-43. doi: 10.1016/j.mito.2012.12.001. Epub 2012 Dec 9.


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.

Keywords: 4′,6-diamidino-2-phenylindole; AR; Bradykinin; CI; DAPI; ETC; F; HEt; Hsp47; KO; MEF; MIM; MOM; Metabolic disorders; MyoD; Nc; OMIM; OXPHOS; Online Mendelian Inheritance in Man; PI; PMF; PS; R123; ROS; Rhodamine 123; Skeletal muscle; Tcf4; electron transport chain; fura-2; heatshock protein 47; hydroethidium; knockout; mitochondrial aspect ratio; mitochondrial complex I or NADH: Ubiquinone oxidoreductase; mitochondrial formfactor; mitochondrial inner membrane; mitochondrial membrane potential; mitochondrial outer membrane; mouse embryonic fibroblast; myoblast determination protein 1; number of mitochondria per cell; oxidative phosphorylation; phosphatidyl serine; propidium iodide; proton-motive force; reactive oxygen species; rhodamine 123; transcription factor 4; wildtype; wt; Δψ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Electron Transport Complex I / deficiency*
  • Fibroblasts / metabolism*
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure*
  • Reactive Oxygen Species / metabolism*


  • Ndufs4 protein, mouse
  • Reactive Oxygen Species
  • Electron Transport Complex I