role of mitochondrial DNA damage in the citotoxicity of reactive oxygen species

• Published in: Journal of bioenergetics and biomembranes 2011-02, Vol.43 (1), p.25-29
• Main Authors: Costa, R. A. P, Romagna, C. D, Pereira, J. L, Souza-Pinto, N. C
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Animals; Antioxidants - metabolism; Biochemistry; Bioorganic Chemistry; Chemistry; Chemistry and Materials Science; DNA damage; DNA Damage - drug effects; DNA, Mitochondrial - genetics; Histology; Humans; Hydrogen-Ion Concentration; methylene blue; Mitochondrial DNA; Models, Genetic; Molecular Structure; Morphology; Organic Chemistry; Oxidative DNA damage; Oxidative stress; Oxidative Stress - physiology; Phosphorylation; Proteins; reactive oxygen species; Reactive Oxygen Species - toxicity; singlet oxygen
• ISSN: 0145-479X; 1573-6881
• DOI: 10.1007/s10863-011-9329-8

Mitochondria contain their own genome, a small circular molecule of around 16.5 kbases. The mitochondrial DNA (mtDNA) encodes for only 13 polypeptides, but its integrity is essential for mitochondrial function, as all 13 proteins are regulatory subunits of the oxidative phosphorylation complexes. Nonetheless, the mtDNA is physically associated with the inner mitochondrial membrane, where the majority of the cellular reactive oxygen species are generated. In fact, the mitochondrial DNA accumulates high levels of oxidized lesions, which have been associated with several pathological and degenerative processes. The cellular responses to nuclear DNA damage have been extensively studied, but so far little is known about the functional outcome and cellular responses to mtDNA damage. In this review we will discuss the mechanisms that lead to damage accumulation and the in vitro models we are establishing to dissect the cellular responses to oxidative damage in the mtDNA and to sort out the differential cellular consequences of accumulation of damage in each cellular genome, the nuclear and the mitochondrial genome.