"ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis"--a critical commentary. Free Radic Biol Med 2008 Nov 01;45(9):1217-9
Date
09/16/2008Pubmed ID
18789385Pubmed Central ID
PMC3595710DOI
10.1016/j.freeradbiomed.2008.07.025Scopus ID
2-s2.0-53449090706 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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.
Author List
Zielonka J, Kalyanaraman BAuthors
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinJacek M. Zielonka PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
DNA, MitochondrialDNA, Neoplasm
Fluorescent Dyes
Gene Expression Regulation, Neoplastic
Humans
Hydrogen Peroxide
Models, Biological
Mutation
Neoplasm Metastasis
Neoplasms
Phenanthridines
Reactive Oxygen Species
Superoxides
