title: "ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis"--a critical commentary.
abstract: In a recent publication (K. Ishikawa et al., 2008, Science320, 661-664), the authors described how replacing the endogenous mitochondrial DNA (mtDNA) in a weakly metastatic mouse tumor cell line with mtDNA from a highly metastatic cell line enhanced tumor progression through enhanced production of reactive oxygen species (ROS). The authors attributed the transformation from a low-metastatic cell line to a high-metastatic phenotype to overproduction of ROS (hydrogen peroxide and superoxide) caused by a dysfunction in mitochondrial complex I protein encoded by mtDNA transferred from the highly metastatic tumor cell line. In this critical evaluation, using the paper by Ishikawa et al. as an example, we bring to the attention of researchers in the free radical field how the failure to appreciate the complexities of dye chemistry could potentially lead to pitfalls, misinterpretations, and erroneous conclusions concerning ROS involvement. Herein we make a case that the authors have failed to show evidence for formation of superoxide and hydrogen peroxide, presumed to be generated from complex I deficiency associated with mtDNA mutations in metastatic cells.
authors.affiliation: Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Jacek
authors.initials: J
authors.lastname: Zielonka
authors.forename: B
authors.initials: B
authors.lastname: Kalyanaraman
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005456:Fluorescent Dyes / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008954:Models, Biological; D009154:Mutation; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010617:Phenanthridines / Q000494:pharmacology; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000494:pharmacology
chemical_list: C521281:5-(6'-triphenylphosphoniumhexyl)-5,6-dihydro-6-phenyl-3,8-phenanthridinediammine; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D010617:Phenanthridines; D017382:Reactive Oxygen Species; D013481:Superoxides; C058428:hydroethidine; D006861:Hydrogen Peroxide
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