The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
A fundamental system of cellular energy homeostasis regulated by PGC-1α
Open accessAbstract
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.
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Cites
Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
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Cited by
Wolf, A., Agnihotri, S., Micallef, J., Mukherjee, J., Sabha, N., Cairns, R., Hawkins, C., & Guha, A. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20101470 · Cited by 789
Transcriptional Control of Mitochondrial Biogenesis and Function
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Mitochondrial Dysfunction in Cancer
Boland, M. L., Chourasia, A. H., & Macleod, K. F. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00292 · Cited by 489
Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance
Davis, J. M., Murphy, E. A., Carmichael, M. D., & Davis, B. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90925.2008 · Cited by 486
The Regulation and Physiology of Mitochondrial Proton Leak
Divakaruni, A. S., & Brand, M. D. (2011) · Physiology · doi:10.1152/physiol.00046.2010 · Cited by 486
Metadata
- Authors
- Rohas, L. M., St-Pierre, J., Uldry, M., Jäger, S., Handschin, C., & Spiegelman, B. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-05-08
- Volume
- 104
- Issue
- 19
- Pages
- 7933-7938
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2017741706
- Cited by
- 208
- References
- 14
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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