Affiliations: Department of Biomedical Sciences, Faculty of Medicine
and Medical Sciences, University of Balamand, Tripoli, Lebanon | MRC Dunn Human Nutrition Unit, Cambridge, UK
Note: [] Address for correspondence: Dr. Karim S. Echtay, Department of
Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of
Balamand, P.O. Box: 100 Tripoli, Lebanon. Tel.: +961 6 930279; Fax: +961 6
930279; E-mail: karim. echtay@balamand.edu.lb
Abstract: In this mini review we summarize recent studies from our laboratory
that show the involvement of superoxide and the lipid peroxidation product
4-hydroxynonenal in the regulation of mitochondrial uncoupling. Superoxide
produced during mitochondrial respiration is a major cause of the cellular
oxidative damage that may underlie degenerative diseases and ageing. Superoxide
production is very sensitive to the magnitude of the mitochondrial protonmotive
force, so can be strongly decreased by mild uncoupling. Superoxide is able to
give rise to other reactive oxygen species, which elicit deleterious effects
primarily by oxidizing intracellular components, including lipids, DNA and
proteins. Superoxide-induced lipid peroxidation leads to the production of
reactive aldehydes, including 4-hydroxynonenal. These aldehydic lipid
peroxidation products are in turn able to modify proteins such as mitochondrial
uncoupling proteins and the adenine nucleotide translocase, converting them
into active proton transporters. This activation induces mild uncoupling and so
diminishes mitochondrial superoxide production, hence protecting against
disease and oxidative damage at the expense of energy production.
