Journal article
Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice
Diabetes (New York, N.Y.), Vol.58(9), pp.1986-1997
09/2009
DOI: 10.2337/db09-0259
PMCID: PMC2731527
PMID: 19542201
Abstract
To elucidate the molecular basis for mitochondrial dysfunction, which has been implicated in the pathogenesis of diabetes complications.
Mitochondrial matrix and membrane fractions were generated from liver, brain, heart, and kidney of wild-type and type 1 diabetic Akita mice. Comparative proteomics was performed using label-free proteome expression analysis. Mitochondrial state 3 respirations and ATP synthesis were measured, and mitochondrial morphology was evaluated by electron microscopy. Expression of genes that regulate mitochondrial biogenesis, substrate utilization, and oxidative phosphorylation (OXPHOS) were determined.
In diabetic mice, fatty acid oxidation (FAO) proteins were less abundant in liver mitochondria, whereas FAO protein content was induced in mitochondria from all other tissues. Kidney mitochondria showed coordinate induction of tricarboxylic acid (TCA) cycle enzymes, whereas TCA cycle proteins were repressed in cardiac mitochondria. Levels of OXPHOS subunits were coordinately increased in liver mitochondria, whereas mitochondria of other tissues were unaffected. Mitochondrial respiration, ATP synthesis, and morphology were unaffected in liver and kidney mitochondria. In contrast, state 3 respirations, ATP synthesis, and mitochondrial cristae density were decreased in cardiac mitochondria and were accompanied by coordinate repression of OXPHOS and peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1alpha transcripts.
Type 1 diabetes causes tissue-specific remodeling of the mitochondrial proteome. Preservation of mitochondrial function in kidney, brain, and liver, versus mitochondrial dysfunction in the heart, supports a central role for mitochondrial dysfunction in diabetic cardiomyopathy.
Details
- Title: Subtitle
- Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice
- Creators
- Heiko Bugger - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USADong ChenChristian RiehleJamie SotoHeather A TheobaldXiao X HuBalasubramanian GanesanBart C WeimerE Dale Abel
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.58(9), pp.1986-1997
- Publisher
- United States
- DOI
- 10.2337/db09-0259
- PMID
- 19542201
- PMCID
- PMC2731527
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- U01HL70525 / NHLBI NIH HHS U01 HL070525 / NHLBI NIH HHS U01 HL087947 / NHLBI NIH HHS U01HL087947 / NHLBI NIH HHS
- Language
- English
- Date published
- 09/2009
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024512402771
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