The production of ROS (reactive oxygen species) by the mitochondrial respiratory chain contributes to a range of pathologies, including neurodegenerative diseases, ischaemia/reperfusion injury and aging. There are also indications that mitochondrial ROS production plays a role in damage response and signal transduction pathways. To unravel the role of mitochondrial ROS production in these processes, we have developed a range of mitochondria-targeted probe molecules. Covalent attachment of a lipophilic cation leads to their accumulation into mitochondria, driven by the membrane potential. Molecules developed so far include antioxidants designed to intercept mitochondrial ROS and reagents that specifically label mitochondrial thiol proteins. Here we outline how mitochondrial ROS formation and its consequences can be investigated using these probes.
Abbreviations used: ΔμH+, proton electrochemical potential gradient; ΔpH, pH gradient; Δψ, membrane potential; Δψm, mitochondrial membrane potential; Δψp, plasma membrane potential; ROS, reactive oxygen species; SOD, superoxide dismutase; MitoQ, mitochondria-targeted ubiquinone; MitoVit E, mitochondria-targeted derivative of α-tocopherol; MitoPBN, mitochondria-targeted derivative of the spin trap PBN (phenyl-t-butylnitrone).
679th Meeting of the Biochemical Society held at the University of Essex, Colchester, 2–4 July 2003