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Trends Pharmacol Sci. 2006 Dec;27(12):639-45. Epub 2006 Oct 23.

Bioenergetics and the formation of mitochondrial reactive oxygen species.

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  • 1Department of Medical Biochemistry, Semmelweis University, Neurobiochemical Group, Hungarian Academy of Sciences, Szentagothai Knowledge Center, Budapest H-1088, Hungary.


The contribution of mitochondria to the manifestation of disease is ascribed largely to the production of reactive oxygen species (ROS), which are obligatory by-products of aerobiosis. Studies using isolated mitochondria have revealed multiple potential sites and circumstances of ROS production but the relevance of these to in situ conditions is limited. In this article, we focus on bioenergetic factors that promote ROS generation at physiologically relevant sites in mitochondria. Emphasis is given to ROS generation by complex I--the first component of the respiratory chain--and to how the NADH:NAD+ ratio regulates ROS formation. Complex I is a physiologically and pathologically relevant ROS-forming site that is important not only in normal mitochondrial energy production but also in the pathogenesis of Parkinson's disease, which is the second most common neurodegenerative disease.

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