Mechanism of the antimycin A-mediated enhancement of t-butylhydroperoxide-induced single-strand breakage in DNA

Andrea Guidarelli, Emilio Clementi, Liliana Brambilla, Orazio Cantoni

Research output: Contribution to journalArticle

Abstract

Inhibitors of complex III increased the DNA strand scission induced by t-butylhydroperoxide (tB-OOH) and cumene hydroperoxide but did not affect DNA damage induced by H2O2. The hypothesis that these effects are selectively linked to inhibition of the electron transport from cytochrome b to cytochrome c1 is validated by the following observations: (1) two complex III inhibitors, antimycin A and 2-heptyl-4-hydroxyquinoline N-oxide, enhanced the tB-OOH-induced DNA cleavage over the same concentration range as that in which inhibition of oxygen consumption was observed; (2) the complex III inhibitor-mediated enhancement of tB-OOH-induced DNA damage was abolished by the complex I inhibitor rotenone or by glucose omission, and (3) the enhancing effects of antimycin A were not observed in respiration-deficient cells. The mechanism whereby the complex III inhibitors potentiate DNA cleavage promoted by tB-OOH was subsequently investigated with intact as well as permeabilized cells. H2O2, produced at the level of mitochondria via a Ca2+-dependent process, was found to account for the enhancing effects of antimycin A.

Original languageEnglish
Pages (from-to)801-806
Number of pages6
JournalBiochemical Journal
Volume328
Issue number3
Publication statusPublished - Dec 15 1997

ASJC Scopus subject areas

  • Biochemistry

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    Guidarelli, A., Clementi, E., Brambilla, L., & Cantoni, O. (1997). Mechanism of the antimycin A-mediated enhancement of t-butylhydroperoxide-induced single-strand breakage in DNA. Biochemical Journal, 328(3), 801-806.