title: Modulation of the conformational state of mitochondrial complex I as a target for therapeutic intervention.
abstract: In recent years, there have been significant advances in our understanding of the functions of mitochondrial complex I other than the generation of energy. These include its role in generation of reactive oxygen species, involvement in the hypoxic tissue response and its possible regulation by nitric oxide (NO) metabolites. In this review, we will focus on the hypoxic conformational change of this mitochondrial enzyme, the so-called active/deactive transition. This conformational change is physiological and relevant to the understanding of certain pathological conditions including, in the cardiovascular system, ischaemia/reperfusion (I/R) damage. We will discuss how complex I can be affected by NO metabolites and will outline some potential mitochondria-targeted therapies in I/R damage.
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 401 East 61st Street, 5th floor, New York, NY 10065, USA; Queens University Belfast, School of Biological Sciences, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Galkin
authors.affiliation: Manchester Cancer Research Centre , University of Manchester , Wilmslow Road, Manchester M20 4QL , UK.
authors.forename: Salvador
authors.initials: S
authors.lastname: Moncada
keywords: ROS; ischaemia/reperfusion; modulation of mitochondrial complex I; nitric oxide; therapeutic intervention