Mitochondrial production of reactive oxygen species: Role of Complex I and quinone analogues

Issue title: The Fifth Conference of the International CoQ10 Association, Kobe 2007 – 50th anniversary of CoQ10 discovery

Article type: Research Article

Authors: Fato, Romana | Bergamini, Christian | Leoni, Serena | Lenaz, Giorgio

Affiliations: Dipartimento di Biochimica "G. Moruzzi", University of Bologna, 40126 Bologna, Italy

Note: [] Corresponding author. E-mail: [email protected]

Abstract: 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 (CoQ_{2}, idebenone and its derivatives), while CoQ_{1}, 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.

Keywords: Complex I, ROS, Complex I inhibitors, short chain quinones, submitochondrial particles

Journal: BioFactors, vol. 32, no. 1-4, pp. 31-39, 2008