Journal article
Mitochondrial impairment is accompanied by impaired oxidative DNA repair in the nucleus
Mutagenesis, Vol.18(6), pp.497-503
2003
DOI: 10.1093/mutage/geg027
PMID: 14614184
Abstract
Depletion of the mitochondrial genome is involved in several human diseases, as well as in mitochondrial diseases induced by drug therapies used in the treatment of cancer and human immunodeficiency virus. In order to identify the molecular changes underlying the pathogenesis of mitochondrial diseases, we determined the oxidative status of a human cell line following depletion of the mitochondrial genome (denoted rho0 cells). Our analysis revealed that rho0 cells contained approximately 10-fold lower levels of superoxide than parental cells (rho+), as detected by oxidation of dihydroethidium. No concurrent decrease in oxidation of hydrogen peroxide, detected using the dye dichloroflorescein diacetate, was observed in rho0 cells. Depletion of the mitochondrial genome did not affect either the expression of superoxide dismutase or its activity. However, catalase expression and its activity decreased in rho0 cells. In addition, glutathione peroxidase activity was higher in rho0 cells compared with rho+. rho0 cells showed increased lipid peroxidation, increased oxidative damage to the nuclear genome and impaired DNA repair. Our data illustrate the importance of the mitochondrial genome and its function to the cellular oxidative environment and nuclear genome instability. It also provides insights into the development of mitochondrial disease as a consequence of cancer therapy.
Details
- Title: Subtitle
- Mitochondrial impairment is accompanied by impaired oxidative DNA repair in the nucleus
- Creators
- Robert L DELSITE - Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 212312, United StatesLene Juel RASMUSSEN - Department of Life Sciences and Chemistry, Roskilde University, 4000 Roskilde, DenmarkAnne Karin RASMUSSEN - Department of Life Sciences and Chemistry, Roskilde University, 4000 Roskilde, DenmarkAmanda KALEN - Free Radical and Radiation Biology Graduate Program, B180 Medical Laboratories, The University of Iowa, Iowa City, IA 52242, United StatesPrabhat C GOSWAMI - Free Radical and Radiation Biology Graduate Program, B180 Medical Laboratories, The University of Iowa, Iowa City, IA 52242, United StatesKeshav K SINGH - Department of Cancer Genetics, Roswell Park Cancer Institute, Cell and Virus Building, Room 247, Elm and Carlton Streets, Buffalo, NY 14263, United States
- Resource Type
- Journal article
- Publication Details
- Mutagenesis, Vol.18(6), pp.497-503
- Publisher
- Oxford University Press; Oxford
- DOI
- 10.1093/mutage/geg027
- PMID
- 14614184
- ISSN
- 0267-8357
- eISSN
- 1464-3804
- Language
- English
- Date published
- 2003
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984047739302771
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