TORC1 specifically inhibits microautophagy through ESCRT-0

Riko Hatakeyama, Claudio De Virgilio* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)
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Nutrient starvation induces the degradation of specific plasma membrane proteins through the multivesicular body (MVB) sorting pathway and of vacuolar membrane proteins through microautophagy. Both of these processes require the gateway protein Vps27, which recognizes ubiquitinated cargo proteins at phosphatidylinositol 3-phosphate-rich membranes as part of a heterodimeric complex coined endosomal sorting complex required for transport 0. The target of rapamycin complex 1 (TORC1), a nutrient-activated central regulator of cell growth, directly phosphorylates Vps27 to antagonize its function in microautophagy, but whether this also serves to restrain MVB sorting at endosomes is still an open question. Here, we show that TORC1 inhibits both the MVB pathway-driven turnover of the plasma membrane-resident high-affinity methionine permease Mup1 and the inositol transporter Itr1 and the microautophagy-dependent degradation of the vacuolar membrane-associated v-ATPase subunit Vph1. Using a Vps277D variant that mimics the TORC1-phosphorylated state of Vps27, we further show that cargo sorting of Vph1 at the vacuolar membrane, but not of Mup1 and Itr1 at endosomes, is sensitive to the TORC1-controlled modifications of Vps27. Thus, TORC1 specifically modulates microautophagy through phosphorylation of Vps27, but controls MVB sorting through alternative mechanisms.

Original languageEnglish
Pages (from-to)1243-1249
Number of pages7
JournalCurrent Genetics
Issue number5
Early online date30 Apr 2019
Publication statusPublished - Oct 2019
Externally publishedYes

Bibliographical note

This work was supported by the Canton of Fribourg and the Swiss National Science Foundation (310030_166474/1; CDV). We thank Christian Ungermann for the GFP-Cps1 strain (Markgraf et al. 2009) and Marie-Pierre Péli-Gulli for critically reading the manuscript.


  • Target of rapamycin complex 1 (TORC1)
  • Endosomal sorting complex required for transport (ESCRT
  • Multivesicular body
  • Microautophagy
  • Vps27


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