title: A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury.
abstract: Ischemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted--ischemia--and then restored--reperfusion--leading to a burst of reactive oxygen species (ROS) from mitochondria. It has been tacitly assumed that ROS production during IR is a non-specific consequence of oxygen interacting with dysfunctional mitochondria upon reperfusion. Recently, this view has changed, suggesting that ROS production during IR occurs by a defined mechanism. Here we survey the metabolic factors underlying IR injury and propose a unifying mechanism for its causes that makes sense of the huge amount of disparate data in this area and provides testable hypotheses and new directions for therapies.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Chouchani
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Pell
authors.affiliation: MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: James
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Work
authors.affiliation: University Department of Surgery and Cambridge NIHR Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Saeb-Parsy
authors.affiliation: MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge, CB2 0XZ, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Frezza
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.affiliation: MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK. Electronic address: mpm@mrc-mbu.cam.ac.uk.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
mesh_terms: D000818:Animals; D004579:Electron Transport; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D015427:Reperfusion Injury / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013438:Sulfhydryl Compounds; D013481:Superoxides