Mitochondrial production of oxygen radical species and the role of Coenzyme Q as an antioxidant.
The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), which is considered as the pathogenic agent of many diseases and of aging. We have investigated the role of complex I in superoxide radical production and found by the combined use of specific inhibitors of complex I that the one-electron donor to oxygen in the complex is a redox center located prior to the sites where three different types of Coenzyme Q (CoQ) competitors bind, to be identified with an Fe-S cluster, most probably N2, or possibly an ubisemiquinone intermediate insensitive to all the above inhibitors. Short-chain Coenzyme Q analogs enhance superoxide formation, presumably by mediating electron transfer from N2 to oxygen. The clinically used CoQ analog, idebenone, is particularly effective, raising doubts on its safety as a drug. Cells counteract oxidative stress by antioxidants. CoQ is the only lipophilic antioxidant to be biosynthesized. Exogenous CoQ, however, protects cells from oxidative stress by conversion into its reduced antioxidant form by cellular reductases. The plasma membrane oxidoreductase and DT-diaphorase are two such systems, likewise, they are overexpressed under oxidative stress conditions.
Genova
Maria Luisa
ML
Dipartimento di Biochimica "G Moruzzi", University of Bologna, 40126 Bologna, Italy.
Pich
Milena Merlo
MM
Biondi
Annalisa
A
Bernacchia
Andrea
A
Falasca
Anna
A
Bovina
Carla
C
Formiggini
Gabriella
G
Parenti Castelli
Giovanna
G
Lenaz
Giorgio
G
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001665:Binding Sites; D004579:Electron Transport / Q000502:physiology; D042967:Electron Transport Complex I; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014451:Ubiquinone / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I