Essential role of the mitochondrial respiratory chain in peroxynitrite-induced strand scission of genomic DNA.

A Guidarelli, I Tommasini, M Fiorani, O Cantoni

Journal: IUBMB life 2001;50(3):195-201

PMID: 11142347

Abstract

A large body of experimental evidence suggests that DNA damage and cytotoxicity mediated by peroxynitrite are linked by a causal relationship and important events in various pathological conditions. In the present study, we investigated the mechanism whereby peroxynitrite causes DNA single strand breakage in intact cells and found that the respiratory chain plays a pivotal role in this response. In particular, peroxynitrite mediates inhibition of complex III and, under these conditions, electrons are directly transferred from ubisemiquinone to molecular oxygen. Hydrogen peroxide produced by the dismutation of superoxides is the species mediating the peroxynitrite-dependent DNA cleavage.

Address: Istituto di Farmacologia e Farmacognosia and Centro di Farmacologia Oncologica Sperimentale, Università degli Studi di Urbino, Italy.

DOI: 10.1080/152165400300001516

Link outs

Free resources

Full Text Sources:

https://onlinelibrary.wiley.com/doi/10.1080/152165...

MeSH Terms: DNA Damage, Electron Transport, Humans, Hydrogen Peroxide, Kinetics, Methacrylates, Mitochondria, Nitrates, Oxygen Consumption, Potassium Cyanide, Rotenone, Thiazoles, U937 Cells