Mitochondrial production of reactive oxygen species: role of complex I and quinone analogues.
Mitochondrial reactive oxygen species (ROS) are mainly produced by the respiratory chain enzymes. The sites for ROS production in mitochondrial respiratory chain are normally ascribed to the activity of Complex I and III. The presence of specific inhibitors modulates reactive oxygen species production in Complex I: inhibitors such as rotenone induce a strong ROS increase, while inhibitors such as stigmatellin prevent it. We have investigated the effect of hydrophilic quinones on Complex I ROS production in presence of different inhibitors. Some short chain quinones are Complex I inhibitors (CoQ2, idebenone and its derivatives), while CoQ1, decylubiquinone~ (DB) and duroquinone (DQ) are good electron acceptors from Complex I. Our results show that the ability of short chain quinones to induce an oxidative stress depends on the site of interaction with Complex I and on their physical-chemical characteristics. We can conclude that hydrophilic quinones may enhance oxidative stress by interaction with the electron escape sites on Complex I while more hydrophobic quinones can be reduced only at the physiological quinone reducing site without reacting with molecular oxygen.
Fato
Romana
R
Dipartimento di Biochimica G. Moruzzi, University of Bologna, 40126 Bologna, Italy. romana.fato@unibo.it
Bergamini
Christian
C
Leoni
Serena
S
Lenaz
Giorgio
G
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002417:Cattle; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000502:physiology*; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology
D017382:Reactive Oxygen Species; D012402:Rotenone; D014451:Ubiquinone; C060262:2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone; D000968:Antimycin A; D042967:Electron Transport Complex I; C025203:Ubiquinone Q1