Mitochondrial oxidative stress causes chromosomal instability of mouse embryonic fibroblasts

Summary Reactive oxygen species are an inevitable by‐product of mitochondrial respiration. It has been estimated that between 0.4 and 4% of molecular oxygen is converted to the radical superoxide () and this level is significantly influenced by the functional status of the mitochondria. It is well e...

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Published inAging cell Vol. 2; no. 5; pp. 277 - 285
Main Authors Samper, E., Nicholls, D. G., Melov, S.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.10.2003
Subjects
Animals
Apoptosis
cancer
Caspase 3
Caspases - metabolism
Cell Division
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Cells, Cultured
Chromosomal Instability
Embryo, Mammalian - cytology
Female
Fibroblasts - cytology
Fibroblasts - metabolism
Fibroblasts - ultrastructure
Mice
mitochondria
Mitochondria - enzymology
Oxidative Stress
Oxygen - physiology
Pregnancy
superoxide dismutase
Superoxide Dismutase - biosynthesis
Superoxide Dismutase - genetics
Superoxide Dismutase - physiology
Translocation, Genetic
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Summary:Summary Reactive oxygen species are an inevitable by‐product of mitochondrial respiration. It has been estimated that between 0.4 and 4% of molecular oxygen is converted to the radical superoxide () and this level is significantly influenced by the functional status of the mitochondria. It is well established that exogenous oxidative stress and high doses of mitochondrial poisons such as paraquat and carbonyl cyanide 4 (trifluoromethoxy) phenylhydrazone (FCCP) can lead to genomic instability. In this report we show for the first time that endogenous mitochondrial oxidative stress in standard cell culture conditions results in nuclear genomic instability in primary mouse embryonic fibroblasts (MEFs). We show that lack of mitochondrial superoxide dismutase in MEFs leads to a severe increase of double strand breaks, end‐to‐end fusions, chromosomal translocations, and loss of cell viability and proliferative capacity. Our results predict that endogenous mitochondrial oxidative stress can induce genomic instability, and therefore may have a profound effect in cancer and aging.
ISSN:1474-9718
1474-9726
DOI:10.1046/j.1474-9728.2003.00062.x