TFEB at a glance

J Cell Sci. 2016 Jul 1;129(13):2475-81. doi: 10.1242/jcs.146365. Epub 2016 Jun 1.

Abstract

The transcription factor EB (TFEB) plays a pivotal role in the regulation of basic cellular processes, such as lysosomal biogenesis and autophagy. The subcellular localization and activity of TFEB are regulated by mechanistic target of rapamycin (mTOR)-mediated phosphorylation, which occurs at the lysosomal surface. Phosphorylated TFEB is retained in the cytoplasm, whereas dephosphorylated TFEB translocates to the nucleus to induce the transcription of target genes. Thus, a lysosome-to-nucleus signaling pathway regulates cellular energy metabolism through TFEB. Recently, in vivo studies have revealed that TFEB is also involved in physiological processes, such as lipid catabolism. TFEB has attracted a lot of attention owing to its ability to induce the intracellular clearance of pathogenic factors in a variety of murine models of disease, such as Parkinson's and Alzheimer's, suggesting that novel therapeutic strategies could be based on the modulation of TFEB activity. In this Cell Science at a Glance article and accompanying poster, we present an overview of the latest research on TFEB function and its implication in human diseases.

Keywords: Autophagy; Lysosomal storage disorders; Lysosomes; MiT family; TFE3; TFEB; mTOR.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Autophagy / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Cell Nucleus / metabolism
  • Energy Metabolism / genetics
  • Humans
  • Lipid Metabolism / genetics
  • Lysosomes / metabolism
  • Metabolism / genetics
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TFEB protein, human
  • TOR Serine-Threonine Kinases