title: Suppressors of superoxide production from mitochondrial complex III.
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.
authors.affiliation: Buck Institute for Research on Aging, Novato, California, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Orr
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Vargas
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Carolina N
authors.initials: CN
authors.lastname: Turk
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Janine E
authors.initials: JE
authors.lastname: Baaten
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Matzen
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Dardov
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Attle
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Quackenbush
authors.affiliation: Buck Institute for Research on Aging, Novato, California, USA.
authors.forename: Renata L S
authors.identifier: http://orcid.org/0000-0002-2031-1522
authors.initials: RL
authors.lastname: Goncalves
authors.affiliation: Buck Institute for Research on Aging, Novato, California, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Perevoshchikova
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: H Michael
authors.initials: HM
authors.lastname: Petrassi
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Meeusen
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California, USA.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Ainscow
authors.affiliation: Buck Institute for Research on Aging, Novato, California, USA.
authors.forename: Martin D
authors.identifier: http://orcid.org/0000-0003-4418-6153
authors.initials: MD
authors.lastname: Brand
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D014450:Electron Transport Complex III / Q000378:metabolism*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D057809:HEK293 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D011720:Pyrazoles; D011743:Pyrimidines; D013481:Superoxides; C032456:antimycin; D000968:Antimycin A; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D014450:Electron Transport Complex III