title: Reverse electron flow-mediated ROS generation in ischemia-damaged mitochondria: role of complex I inhibition vs. depolarization of inner mitochondrial membrane.
abstract: BACKGROUND
  The reverse electron flow-induced ROS generation (RFIR) is decreased in ischemia-damaged mitochondria. Cardiac ischemia leads to decreased complex I activity and depolarized inner mitochondrial membrane potential (ΔΨ) that are two key factors to affect the RFIR in isolated mitochondria. We asked if a partial inhibition of complex I activity without alteration of the ΔΨ is able to decrease the RFIR.
  
  
  METHODS
  Cardiac mitochondria were isolated from mouse heart (C57BL/6) with and without ischemia. The rate of H2O2 production from mitochondria was determined using amplex red coupled with horseradish peroxidase. Mitochondria were isolated from the mitochondrial-targeted STAT3 overexpressing mouse (MLS-STAT3E) to clarify the role of partial complex I inhibition in RFIR production.
  
  
  RESULTS
  The RFIR was decreased in ischemia-damaged mouse heart mitochondria with decreased complex I activity and depolarized ΔΨ. However, the RFIR was not altered in the MLS-STAT3E heart mitochondria with complex I defect but without depolarization of the ΔΨ. A slight depolarization of the ΔΨ in wild type mitochondria completely eliminated the RFIR.
  
  
  CONCLUSIONS
  The mild uncoupling but not the partially decreased complex I activity contributes to the observed decrease in RFIR in ischemia-damaged mitochondria.
  
  
  CONCLUSIONS
  The RFIR is less likely to be a key source of cardiac injury during reperfusion.
authors.affiliation: Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ross
authors.forename: Karol
authors.initials: K
authors.lastname: Szczepanek
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bowler
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Andrew
authors.initials: A
authors.lastname: Larner
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lesnefsky
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I
keywords: Electron transport chain; Ischemia; Reactive oxygen species; STAT3