Premium
Essential Role of the Mitochondrial Respiratory Chain in Peroxynitrite‐Induced Strand Scission of Genomic DNA
Author(s) -
Guidarelli Andrea,
Tommasini Ilaria,
Fiorani Mara,
Cantoni Orazio
Publication year - 2000
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/152165400300001516
Subject(s) - peroxynitrite , dna , chemistry , hydrogen peroxide , superoxide , dna damage , biophysics , microbiology and biotechnology , reactive oxygen species , peroxide , cytotoxicity , peroxynitrous acid , biochemistry , biology , in vitro , enzyme , organic chemistry
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.