title: Mitochondrial Complex I decrease is responsible for bioenergetic dysfunction in K-ras transformed cells.
abstract: Many cancer cells are characterized by high rate of glycolysis and reduced rate of aerobic respiration, whose mechanism is still elusive. Here we investigate the down-regulation of oxidative phosphorylation (OXPHOS) in K-ras transformed mouse fibroblasts as compared to a control counterpart. Transcriptional analysis showed different expression levels of several OXPHOS nuclear genes in the two cell lines. In particular, during the exponential growth phase most genes encoding proteins of Complex I were expressed at lower levels in transformed cells. Consistently, a significant decrease of Complex I content was found in transformed cells. Moreover, analysis of NAD-dependent respiration and ATP synthesis indicated a strong decrease of Complex I activity in the mitochondria from neoplastic cells, that was confirmed by direct assay of the enzyme redox activity. At variance, succinate-dependent respiration and ATP synthesis were not significantly affected. Taken together, our results provide the new insight that the reduction of respiration observed in K-ras transformed cells is specifically due to a Complex I activity decrease.
authors.affiliation: Department of Biochemistry "G. Moruzzi", University of Bologna, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baracca
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Chiaradonna
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sgarbi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Solaini
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lenaz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D019069:Cell Respiration / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D042967:Electron Transport Complex I / Q000737:chemistry* / Q000378:metabolism*; D004734:Energy Metabolism; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D011905:Genes, ras; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I; D010100:Oxygen