| Title | Suppressors of superoxide production from mitochondrial complex III. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Orr 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 |
| Journal | Nat Chem Biol |
| Volume | 11 |
| Issue | 11 |
| Pagination | 834-6 |
| Date Published | 2015 Nov |
| ISSN | 1552-4469 |
| Keywords | Adenosine 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. |
| DOI | 10.1038/nchembio.1910 |
| Alternate Journal | Nat. Chem. Biol. |
| PubMed ID | 26368590 |
| PubMed Central ID | PMC4618194 |
| Grant List | R01 AG033542 / AG / NIA NIH HHS / United States TL1 AG032116 / AG / NIA NIH HHS / United States |