Multistep regulation of TFEB by MTORC1

Silvia Vega-Rubin-de-Celis, Samuel Peña-Llopis, Meghan Konda, James Brugarolas

Research output: Contribution to journalArticlepeer-review

136 Scopus citations


The master regulator of lysosome biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEBS211A localizes diffusely in both cytoplasm and nucleus and, as we show, retains regulation by MTORC1. Here, we report that endogenous TFEB is phosphorylated at S122 in an MTORC1-dependent manner, that S122 is phosphorylated in vitro by recombinant MTOR, and that S122 is important for TFEB regulation by MTORC1. Specifically, nuclear localization following MTORC1 inhibition is blocked by a S122D mutation (despite S211 dephosphorylation). Furthermore, such a mutation inhibits lysosomal biogenesis induced by Torin1. These data reveal a novel mechanism of TFEB regulation by MTORC1 essential for lysosomal biogenesis.

Original languageEnglish (US)
Pages (from-to)464-472
Number of pages9
Issue number3
StatePublished - Mar 4 2017


  • Lysosomal biogenesis
  • MTOR
  • TFEB
  • YWHA
  • subcellular localization

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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