A fundamental system of cellular energy homeostasis regulated by PGC-1α

Rohas, L. M. and St-Pierre, J. and Uldry, M. and Jager, S. and Handschin, C. and Spiegelman, B. M.. (2007) A fundamental system of cellular energy homeostasis regulated by PGC-1α. Proceedings of the National Academy of Sciences of the United States of America, 104 (19). pp. 7933-7938.

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Official URL: http://edoc.unibas.ch/dok/A5258715

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Maintenance of ATP levels is a critical feature of all cells. Mitochondria are responsible for most ATP synthesis in eukaryotes. We show here that mammalian cells respond to a partial chemical uncoupling of mitochondrial oxidative phosphorylation with a decrease in ATP levels, which recovers over several hours to control levels. This recovery occurs through an increased expression of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1α (PGC-1α) and mitochondrial genes. Cells and animals lacking PGC-1α lose this compensatory mechanism and cannot defend their ATP levels or increase mitochondrial gene expression in response to reduced oxidative phosphorylation. The induction of PGC-1α and its mitochondrial target genes is triggered by a burst of intracellular calcium, which causes an increase in cAMP-response-element-binding protein and transducer of regulated cAMP-response-element-binding proteins actions on the PGC-1α promoter. These data illustrate a fundamental transcriptional cycle that provides homeostatic control of cellular ATP. In light of this compensatory system that limits the toxicity of mild uncoupling, the use of chemical uncoupling of mitochondria as a means of treating obesity should be re-evaluated.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
UniBasel Contributors:Handschin, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Mar 2019 11:27
Deposited On:22 Mar 2012 13:20

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