Suppressors of superoxide production from mitochondrial complex III

Nat Chem Biol. 2015 Nov;11(11):834-6. doi: 10.1038/nchembio.1910. Epub 2015 Sep 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Antimycin A / analogs & derivatives
  • Antimycin A / antagonists & inhibitors
  • Antimycin A / pharmacology
  • Dose-Response Relationship, Drug
  • Electron Transport Complex III / metabolism*
  • Female
  • Free Radical Scavengers / pharmacology*
  • HEK293 Cells
  • High-Throughput Screening Assays
  • Humans
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Phosphorylation / drug effects
  • Oxidative Stress
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Signal Transduction
  • Superoxides / antagonists & inhibitors*
  • Superoxides / metabolism

Substances

  • Free Radical Scavengers
  • Pyrazoles
  • Pyrimidines
  • Superoxides
  • antimycin
  • Antimycin A
  • Adenosine Triphosphate
  • Hydrogen Peroxide
  • Electron Transport Complex III

Associated data

  • PubChem-Substance/252211225
  • PubChem-Substance/252211226
  • PubChem-Substance/252211227
  • PubChem-Substance/252211228
  • PubChem-Substance/252211229
  • PubChem-Substance/252211230
  • PubChem-Substance/252211231
  • PubChem-Substance/252211232
  • PubChem-Substance/252211233
  • PubChem-Substance/252211234
  • PubChem-Substance/252211235
  • PubChem-Substance/252211236
  • PubChem-Substance/252211237
  • PubChem-Substance/252211238
  • PubChem-Substance/252211239
  • PubChem-Substance/252211240
  • PubChem-Substance/252211241
  • PubChem-Substance/252211242