Transcriptional Control of Cardiac Fuel Metabolism and Mitochondrial Function
| العنوان: | Transcriptional Control of Cardiac Fuel Metabolism and Mitochondrial Function |
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| المؤلفون: | T.C. Leone, D.P. Kelly |
| المصدر: | Cold Spring Harbor Symposia on Quantitative Biology. 76:175-182 |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Genetics, Regulation of gene expression, Transcription, Genetic, Myocardium, Gene targeting, Mitochondrion, Biology, medicine.disease, Biochemistry, Article, Mitochondria, Heart, Cell biology, Gene Expression Regulation, Mitochondrial biogenesis, Heart failure, Transcriptional regulation, medicine, Animals, Humans, Energy Metabolism, Molecular Biology, Transcription factor, Heart metabolism, Transcription Factors |
| الوصف: | As a persistent pump, the mammalian heart demands a high-capacity mitochondrial system. Significant progress has been made in delineating the gene regulatory networks that control mitochondrial biogenesis and function in striated muscle. The PPARγ coactivator-1 (PGC-1) coactivators serve as inducible boosters of downstream transcription factors that control the expression of genes involved in mitochondrial energy transduction, ATP synthesis, and biogenesis. PGC-1 gain-of-function and loss-of-function studies targeting two PGC-1 family members, PGC-1α and PGC-1β, have provided solid evidence that these factors are both necessary and sufficient for perinatal mitochondrial biogenesis and maintenance of high-capacity mitochondrial function in postnatal heart. In humans, during the development of heart failure owing to hypertension or obesity-related diabetes, the activity of the PGC-1 coactivators, and several downstream target transcription factors, is altered. Gene targeting studies in mice have demonstrated that loss of PGC-1α and PGC-1β in heart leads to heart failure. Interestingly, the pattern of dysregulation within the PGC-1 transcriptional regulatory circuit distinguishes the heart disease caused by hypertension from that caused by diabetes. This transcriptional regulatory cascade and downstream metabolic pathways should be considered as targets for novel etiology-specific therapeutics aimed at the early stages of heart failure. |
| تدمد: | 1943-4456 0091-7451 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c3dd1c50c9b28027edea572afd6dac8dTest https://doi.org/10.1101/sqb.2011.76.011965Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c3dd1c50c9b28027edea572afd6dac8d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19434456 00917451 |
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