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. GENERAL SIGNIFICANCE: The RFIR is less likely to be a key source of cardiac injury during reperfusion.
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. GENERAL SIGNIFICANCE: The RFIR is less likely to be a key source of cardiac injury during reperfusion.
Authors: Karol Szczepanek; Qun Chen; Marta Derecka; Fadi N Salloum; Qifang Zhang; Magdalena Szelag; Joanna Cichy; Rakesh C Kukreja; Jozef Dulak; Edward J Lesnefsky; Andrew C Larner Journal: J Biol Chem Date: 2011-06-29 Impact factor: 5.157
Authors: Casey L Quinlan; Adam L Orr; Irina V Perevoshchikova; Jason R Treberg; Brian A Ackrell; Martin D Brand Journal: J Biol Chem Date: 2012-06-11 Impact factor: 5.157
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Authors: Namrata Tomar; Xiao Zhang; Sunil M Kandel; Shima Sadri; Chun Yang; Mingyu Liang; Said H Audi; Allen W Cowley; Ranjan K Dash Journal: Biochim Biophys Acta Bioenerg Date: 2021-12-03 Impact factor: 3.991