title: Mitochondrial dysfunction in cardiac ischemia-reperfusion injury: ROS from complex I, without inhibition.
abstract: A key pathologic event in cardiac ischemia reperfusion (I-R) injury is mitochondrial energetic dysfunction, and several studies have attributed this to complex I (CxI) inhibition. In isolated perfused rat hearts, following I-R, we found that CxI-linked respiration was inhibited, but isolated CxI enzymatic activity was not. Using the mitochondrial thiol probe iodobutyl-triphenylphosphonium in conjunction with proteomic tools, thiol modifications were identified in several subunits of the matrix-facing 1alpha sub-complex of CxI. These thiol modifications were accompanied by enhanced ROS generation from CxI, but not complex III. Implications for the pathology of cardiac I-R injury are discussed.
authors.affiliation: Departments of Anesthesiology, and Biochemistry & Molecular Biology, Box 604, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester NY 14642, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tompkins
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Burwell
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Digerness
authors.forename: Corinne
authors.initials: C
authors.lastname: Zaragoza
authors.forename: William L
authors.initials: WL
authors.lastname: Holman
authors.forename: Paul S
authors.initials: PS
authors.lastname: Brookes
mesh_terms: D000818:Animals; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; C002744:3-nitrotyrosine; D014443:Tyrosine; D042967:Electron Transport Complex I