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Suppressors of superoxide production from mitochondrial complex III.

TitleSuppressors of superoxide production from mitochondrial complex III.
Publication TypeJournal Article
Year of Publication2015
AuthorsOrr AL, Vargas L, Turk CN, Baaten JE, Matzen JT, Dardov VJ, Attle SJ, Li J, Quackenbush DC, Goncalves RLS, Perevoshchikova IV, H Petrassi M, Meeusen SL, Ainscow EK, Brand MD
JournalNat Chem Biol
Volume11
Issue11
Pagination834-6
Date Published2015 Nov
ISSN1552-4469
KeywordsAdenosine Triphosphate, Animals, Antimycin A, Dose-Response Relationship, Drug, Electron Transport Complex III, Female, Free Radical Scavengers, HEK293 Cells, High-Throughput Screening Assays, Humans, Hydrogen Peroxide, Insulin-Secreting Cells, Male, Mitochondria, Oxidative Phosphorylation, Oxidative Stress, Pyrazoles, Pyrimidines, Rats, Rats, Sprague-Dawley, Rats, Wistar, Signal Transduction, Superoxides
Abstract

Mitochondrial electron transport drives ATP synthesis but also generates reactive oxygen species, which are both cellular signals and damaging oxidants. Superoxide production by respiratory complex III is implicated in diverse signaling events and pathologies, but its role remains controversial. Using high-throughput screening, we identified compounds that selectively eliminate superoxide production by complex III without altering oxidative phosphorylation; they modulate retrograde signaling including cellular responses to hypoxic and oxidative stress.

DOI10.1038/nchembio.1910
Alternate JournalNat. Chem. Biol.
PubMed ID26368590
PubMed Central IDPMC4618194
Grant ListR01 AG033542 / AG / NIA NIH HHS / United States
TL1 AG032116 / AG / NIA NIH HHS / United States