P3480Tissue-specific regulation of the mitochondrial proteome by adiponectin receptor 1
| Autor: | C. Bode, Katharina Pfeil, Mark E Pepin, Andreas Zirlik, Adam R. Wende, Christoph Koentges, Heiko Bugger, Johannes Gollmer |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | European Heart Journal. 40 |
| ISSN: | 1522-9645 0195-668X |
| DOI: | 10.1093/eurheartj/ehz745.0350 |
| Popis: | Lack of the adiponectin target receptor adiponectin receptor 1 (AdipoR1) impairs gene expression of mitochondrial OXPHOS proteins due to impaired AMPK-SIRT1-PGC-1α signaling. Since decreased adiponectin serum levels in diabetes mellitus should thus compromise AdipoR1 signaling, we hypothesized that impaired AdipoR1 signaling may causally contribute to typically observed mitochondrial defects in diabetes complications. Thus, we performed comparative proteomics in cardiac, renal and hepatic tissue of AdipoR1−/− mice using LC-MS/MS. Using principal component analysis, heatmapping and hierarchical clustering, a significant separation of genotypes was observed across tissues. Enrichment analysis of differentially expressed proteins revealed disproportionate representation of proteins involved in oxidative phosphorylation, TCA cycle and fatty acid oxidation in all tissues. While 121 or 98 or 78 proteins were differentially regulated in cardiac or renal or hepatic tissue, respectively, only 15 proteins were regulated in the same direction across all tissues. Pathway analysis identified HNF4, NRF1, LONP, RICTOR, SURF1, insulin receptor and PGC-1α as most likely upstream regulators. Importantly, we found a dramatic downregulation of AdipoR1 expression in heart (−70%), liver (−90%) and kidney (−80%; all p |
| Databáze: | OpenAIRE |
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