| Mitochondrial dysfunction in the type 2 diabetic heart is associated with alterations in spatially distinct mitochondrial proteomes. | |
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MedLine Citation:
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PMID: 20543078 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiac complications and heart failure are the leading cause of death in type 2 diabetic patients. Mitochondrial dysfunction is central in the pathogenesis of the type 2 diabetic heart. However, it is unclear whether this dysfunction is specific for a particular subcellular region. The purpose of this study was to determine whether mitochondrial dysfunction in the type 2 diabetic heart is specific to a spatially distinct subset of mitochondria. We investigated mitochondrial morphology, function, and proteomic composition of subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) in 18-wk-old db/db mice. Oxidative damage was assessed in subpopulations through the measurement of lipid peroxidation byproducts and nitrotyrosine residues. Proteomic profiles and posttranslational modifications were assessed in mitochondrial subpopulations using iTRAQ and multi-dimensional protein identification technologies, respectively. SSM from db/db hearts had altered morphology, including a decrease in size and internal complexity, whereas db/db IFM were increased in internal complexity. Db/db SSM displayed decreased state 3 respiration rates, electron transport chain activities, ATP synthase activities, and mitochondrial membrane potential and increased oxidative damage, with no change in IFM. Proteomic assessment revealed a greater impact on db/db SSM compared with db/db IFM. Inner mitochondrial membrane proteins, including electron transport chain, ATP synthesis, and mitochondrial protein import machinery, were predominantly decreased. We provide evidence that mitochondrial dysfunction in the type 2 diabetic heart is associated with a specific subcellular locale. Furthermore, mitochondrial morphological and functional indexes are impacted differently during type 2 diabetic insult and may result from the modulation of spatially distinct mitochondrial proteomes. |
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Authors:
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Erinne R Dabkowski; Walter A Baseler; Courtney L Williamson; Matthew Powell; Trust T Razunguzwa; Jefferson C Frisbee; John M Hollander |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-06-11 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-30 Completed Date: 2010-08-30 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H529-40 Citation Subset: IM |
Affiliation:
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West Virginia Univ. School of Medicine, Div. of Exercise Physiology, Center for Cardiovascular and Respiratory Sciences, 1 Medical Center Dr., Morgantown, WV 26506, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / metabolism Cell Respiration Diabetes Mellitus, Type 2 / genetics, metabolism*, pathology Disease Models, Animal Electron Transport Electron Transport Chain Complex Proteins / metabolism Ion Channels / metabolism Lipid Peroxidation Male Membrane Potential, Mitochondrial Mice Mitochondria, Heart / metabolism*, pathology Mitochondrial ADP, ATP Translocases / metabolism Mitochondrial Proteins / metabolism* Mitochondrial Proton-Translocating ATPases / metabolism Mitochondrial Size Oxidative Stress Protein Processing, Post-Translational Proteome* Proteomics / methods Tyrosine / analogs & derivatives, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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RR-020866/RR/NCRR NIH HHS; RR-16440/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Electron Transport Chain Complex Proteins; 0/Ion Channels; 0/Mitochondrial Proteins; 0/Proteome; 0/mitochondrial uncoupling protein 3; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 9068-80-8/Mitochondrial ADP, ATP Translocases; EC 3.6.3.-/Mitochondrial Proton-Translocating ATPases |
| Comments/Corrections | |
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