Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bugger, H; Chen, D; Riehle, C; Soto, J; Theobald, HA; Hu, XX; Ganesan, B; Weimer, BC; Abel, ED.
Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice.
Diabetes. 2009; 58(9): 1986-1997.
Doi: 10.2337/db09-0259
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- Führende Autor*innen der Med Uni Graz
- Bugger Heiko Matthias
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenosine Triphosphate - metabolism
- Animals -
- Brain - metabolism
- Cell Respiration -
- Diabetes Complications - genetics
- Diabetes Complications - metabolism
- Diabetes Mellitus, Type 1 - genetics
- Diabetes Mellitus, Type 1 - metabolism
- Fatty Acids - metabolism
- Gene Expression Profiling -
- Kidney - metabolism
- Liver - metabolism
- Male -
- Mice -
- Mice, Inbred C57BL -
- Mice, Mutant Strains -
- Microscopy, Electron -
- Mitochondria, Liver - genetics
- Mitochondria, Liver - metabolism
- Mitochondria, Liver - ultrastructure
- Mitochondrial Diseases - genetics
- Mitochondrial Diseases - metabolism
- Oxidative Phosphorylation -
- Proteome - metabolism