title: Proteome and cytoskeleton responses in osteosarcoma cells with reduced OXPHOS activity.
abstract: We have recently shown disorganization of the vimentin network in cultured cells deficient in oxidative phosphorylation (OXPHOS). We describe here the cellular responses to OXPHOS deficiency in osteosarcoma cells upon complex I (CI) and complex IV (CIV) inhibition, and upon the lack of mitochondrial DNA (rho0 cells). We examined the cytoskeletal organization and the distribution of mitochondria and analysed total proteome by 2-DE and vimentin expression by ELISA. Upon CIV inhibition and in rho0 cells, the vimentin network had collapsed around the nucleus and formed thick bundles. The mitochondria formed a perinuclear crescent upon CIV inhibition, whereas they accumulated around the nucleus in the rho0 cells, where the amount of vimentin was increased. Analysis of the total proteome revealed that a lack of mitochondrial DNA or inhibition of CI or CIV led to changes in the expression of cytoskeletal and cytoskeleton-associated proteins and proteins involved in apoptosis, OXPHOS, glycolysis, the tricarboxylic acid cycle, and oxidative stress responses. Our findings suggest that a deficiency in the energy converting system and oxidative stress can lead to cytoskeletal changes.
authors.affiliation: Department of Neurology, University of Oulu, Oulu, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Annunen-Rasila
authors.forename: Steffen
authors.initials: S
authors.lastname: Ohlmeier
authors.forename: Hanna
authors.initials: H
authors.lastname: Tuokko
authors.forename: Johanna
authors.initials: J
authors.lastname: Veijola
authors.forename: Kari
authors.initials: K
authors.lastname: Majamaa
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000502:physiology; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D019810:Sodium Azide / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D011506:Proteins; D020543:Proteome; D014746:Vimentin; D012402:Rotenone; D019810:Sodium Azide; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I