TORC1 regulates autophagy induction in response to proteotoxic stress in yeast and human cells

Biochem Biophys Res Commun. 2019 Apr 2;511(2):434-439. doi: 10.1016/j.bbrc.2019.02.077. Epub 2019 Feb 21.


Misfolded and aggregated proteins are eliminated to maintain protein homeostasis. Autophagy contributes to the removal of protein aggregates. However, if and how proteotoxic stress induces autophagy is poorly understood. Here we show that proteotoxic stress after treatment with azetidine-2-carboxylic acid (AZC), a toxic proline analog, induces autophagy in budding yeast. AZC treatment attenuated target of rapamycin complex 1 (TORC1) activity, resulting in the dephosphorylation of Atg13, a key factor of autophagy. By contrast, AZC treatment did not affect target of rapamycin complex 2 (TORC2). Proteotoxic stress also induced TORC1 inactivation and autophagy in fission yeast and human cells. This study suggested that TORC1 is a conserved key factor to cope with proteotoxic stress in eukaryotic cells.

Keywords: Autophagy; Azetidine-2-carboxylic acid (AZC); Proteotoxic stress; Target of rapamycin complex 1 (TORC1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / drug effects*
  • Azetidinecarboxylic Acid / toxicity*
  • Fungal Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects*
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / drug effects*


  • Fungal Proteins
  • Azetidinecarboxylic Acid
  • Mechanistic Target of Rapamycin Complex 1