Suppressors of superoxide production from mitochondrial complex III

September 14th, 2015 by Adam L Orr

Nature Chemical Biology 11, 834 (2015). doi:10.1038/nchembio.1910

Authors: Adam L Orr, Leonardo Vargas, Carolina N Turk, Janine E Baaten, Jason T Matzen, Victoria J Dardov, Stephen J Attle, Jing Li, Douglas C Quackenbush, Renata L S Goncalves, Irina V Perevoshchikova, H Michael Petrassi, Shelly L Meeusen, Edward K Ainscow & Martin D Brand

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.