Author: ["Emilie Blanchet","Jean-Sébastien Annicotte","Sylviane Lagarrigue","Victor Aguilar","Cyrielle Clapé","Carine Chavey","Vanessa Fritz","François Casas","Florence Apparailly","Johan Auwerx","Lluis Fajas"]
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Abstract
E2F is known to regulate the cell cycle, but Fajas and colleagues now show that E2F acts as a switch to allow cells to adapt to stressful metabolic conditions. Under basal conditions, E2F promotes cell-cycle progression and represses transcription of genes required for mitochondrial oxidative metabolism; however, this repression is alleviated on energy starvation. Cells respond to stress by coordinating proliferative and metabolic pathways. Starvation restricts cell proliferative (glycolytic) and activates energy productive (oxidative) pathways. Conversely, cell growth and proliferation require increased glycolytic and decreased oxidative metabolism levels1. E2F transcription factors regulate both proliferative and metabolic genes2,3. E2Fs have been implicated in the G1/S cell-cycle transition, DNA repair, apoptosis, development and differentiation2,3,4. In pancreatic β-cells, E2F1 gene regulation facilitated glucose-stimulated insulin secretion5,6. Moreover, mice lacking E2F1 (E2f1−/−) were resistant to diet-induced obesity4. Here, we show that E2F1 coordinates cellular responses by acting as a regulatory switch between cell proliferation and metabolism. In basal conditions, E2F1 repressed key genes that regulate energy homeostasis and mitochondrial functions in muscle and brown adipose tissue. Consequently, E2f1−/− mice had a marked oxidative phenotype. An association between E2F1 and pRB was required for repression of genes implicated in oxidative metabolism. This repression was alleviated in a constitutively active CDK4 (CDK4R24C) mouse model or when adaptation to energy demand was required. Thus, E2F1 represents a metabolic switch from oxidative to glycolytic metabolism that responds to stressful conditions.Cite this article
Blanchet, E., Annicotte, JS., Lagarrigue, S. et al. E2F transcription factor-1 regulates oxidative metabolism. Nat Cell Biol 13, 1146–1152 (2011). https://doi.org/10.1038/ncb2309 