| Proteomic alterations of distinct mitochondrial subpopulations in the type 1 diabetic heart: contribution of protein import dysfunction. | |
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MedLine Citation:
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PMID: 21048079 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Diabetic cardiomyopathy is associated with increased risk of heart failure in type 1 diabetic patients. Mitochondrial dysfunction is suggested as an underlying contributor to diabetic cardiomyopathy. Cardiac mitochondria are characterized by subcellular spatial locale, including mitochondria located beneath the sarcolemma, subsarcolemmal mitochondria (SSM), and mitochondria situated between the myofibrils, interfibrillar mitochondria (IFM). The goal of this study was to determine whether type 1 diabetic insult in the heart influences proteomic make-up of spatially distinct mitochondrial subpopulations and to evaluate the role of nuclear encoded mitochondrial protein import. Utilizing multiple proteomic approaches (iTRAQ and two-dimensional-differential in-gel electrophoresis), IFM proteomic make-up was impacted by type 1 diabetes mellitus to a greater extent than SSM, as evidenced by decreased abundance of fatty acid oxidation and electron transport chain proteins. Mitochondrial phosphate carrier and adenine nucleotide translocator, as well as inner membrane translocases, were decreased in the diabetic IFM (P < 0.05 for both). Mitofilin, a protein involved in cristae morphology, was diminished in the diabetic IFM (P < 0.05). Posttranslational modifications, including oxidations and deamidations, were most prevalent in the diabetic IFM. Mitochondrial heat shock protein 70 (mtHsp70) was significantly decreased in diabetic IFM (P < 0.05). Mitochondrial protein import was decreased in the diabetic IFM with no change in the diabetic SSM (P < 0.05). Taken together, these results indicate that mitochondrial proteomic alterations in the type 1 diabetic heart are more pronounced in the IFM. Further, proteomic alterations are associated with nuclear encoded mitochondrial protein import dysfunction and loss of an essential mitochondrial protein import constituent, mtHsp70, implicating this process in the pathogenesis of the diabetic heart. |
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Authors:
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Walter A Baseler; Erinne R Dabkowski; Courtney L Williamson; Tara L Croston; Dharendra Thapa; Matthew J Powell; Trust T Razunguzwa; John M Hollander |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-03 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 300 ISSN: 1522-1490 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-03 Completed Date: 2011-04-05 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R186-200 Citation Subset: IM |
Affiliation:
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West Virginia University School of Medicine, Division 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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3-Hydroxyacyl CoA Dehydrogenases
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metabolism Acetyl-CoA C-Acyltransferase / metabolism Animals Blood Glucose / metabolism Carbon-Carbon Double Bond Isomerases / metabolism Carrier Proteins / genetics, metabolism Citric Acid Cycle / physiology Diabetes Mellitus, Experimental / blood, metabolism*, physiopathology Diabetes Mellitus, Type 1 / blood, metabolism*, physiopathology Diabetic Cardiomyopathies / metabolism*, physiopathology Down-Regulation / physiology Electron Transport Chain Complex Proteins / metabolism Enoyl-CoA Hydratase / metabolism Gene Expression / physiology HSP70 Heat-Shock Proteins / metabolism Heart / physiopathology Insulin / blood Male Membrane Potential, Mitochondrial / physiology Mice Mice, Inbred Strains Mitochondria, Heart / metabolism* Mitochondrial Proteins / genetics, metabolism Muscle Proteins / metabolism Myocardium / metabolism* Protein Processing, Post-Translational / physiology Protein Transport / physiology* Proteome / genetics, metabolism* Proteomics Racemases and Epimerases / metabolism Recombinant Fusion Proteins / metabolism Up-Regulation / physiology |
| Grant Support | |
ID/Acronym/Agency:
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DP2DK083095/DK/NIDDK NIH HHS; RR020866/RR/NCRR NIH HHS; RR16440/RR/NCRR NIH HHS; T32HL090610/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Carrier Proteins; 0/Electron Transport Chain Complex Proteins; 0/HSP70 Heat-Shock Proteins; 0/Insulin; 0/Mitochondrial Proteins; 0/Muscle Proteins; 0/Proteome; 0/Recombinant Fusion Proteins; 0/fatty acid oxidation complex; 0/mitofilin protein, mouse; EC 1.1.1.35/3-Hydroxyacyl CoA Dehydrogenases; EC 2.3.1.16/Acetyl-CoA C-Acyltransferase; EC 4.2.1.17/Enoyl-CoA Hydratase; EC 5.1.-/Racemases and Epimerases; EC 5.3.3.-/Carbon-Carbon Double Bond Isomerases |
| Comments/Corrections | |
Comment In:
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Am J Physiol Regul Integr Comp Physiol. 2011 Feb;300(2):R183-5
[PMID:
21123761
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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