TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop
- 31 May 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 15 (6), 647-+
- https://doi.org/10.1038/ncb2718
Abstract
The lysosomal autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the transcriptional regulation of this pathway in response to metabolic cues is uncharacterized. Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc 1 alpha and Ppar 1 alpha. Thus, during starvation a transcriptional mechanism links the autophagic pathway to cellular energy metabolism. The conservation of this mechanism in Caenorhabditis elegans suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation. Viral delivery of TFEB to the liver prevented weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity, suggesting a new therapeutic strategy for disorders of lipid metabolism.This publication has 57 references indexed in Scilit:
- A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEBThe EMBO Journal, 2012
- A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesisNature, 2012
- Autophagy in the Cellular Energetic BalanceCell Metabolism, 2011
- Defective Hepatic Autophagy in Obesity Promotes ER Stress and Causes Insulin ResistanceCell Metabolism, 2010
- C. elegans Major Fats Are Stored in Vesicles Distinct from Lysosome-Related OrganellesCell Metabolism, 2009
- A Multiparameter Network Reveals Extensive Divergence between C. elegans bHLH Transcription FactorsCell, 2009
- Autophagy regulates lipid metabolismNature, 2009
- Endocrine Regulation of the Fasting Response by PPARα-Mediated Induction of Fibroblast Growth Factor 21Cell Metabolism, 2007
- Proteolytic and lipolytic responses to starvationNutrition, 2006
- Arresting development arrests aging in the nematode Caenorhabditis elegansMechanisms of Ageing and Development, 1984