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.
MeSH terms
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Animals
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Electron Transport Complex I / antagonists & inhibitors
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Electron Transport Complex I / chemistry
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Electron Transport Complex I / metabolism*
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Male
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Mitochondria, Heart / metabolism*
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Mitochondria, Heart / pathology*
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Myocardial Ischemia / metabolism
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Myocardial Ischemia / pathology
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Myocardial Ischemia / physiopathology*
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Myocardial Reperfusion Injury / metabolism
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Myocardial Reperfusion Injury / pathology
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Myocardial Reperfusion Injury / physiopathology*
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Proteomics
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species / metabolism*
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Sulfhydryl Compounds / chemistry
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Sulfhydryl Compounds / metabolism
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Tyrosine / analogs & derivatives
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Tyrosine / metabolism
Substances
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Reactive Oxygen Species
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Sulfhydryl Compounds
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3-nitrotyrosine
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Tyrosine
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Electron Transport Complex I