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Updated: Aug 7, 2025

Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.2K

The TORC1 activates Rpd3L complex to deacetylate Ino80 and H2A.Z and repress autophagy

Xin Li1, Qianyun Mei1, Qi Yu1

  • 1State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei 430062, China.

Science Advances
|March 8, 2023
PubMed

Insights

The Rpd3L complex regulates autophagy by deacetylating Ino80 and H2A.Z, controlling gene expression in response to nutrient availability. This process is modulated by the target of rapamycin complex 1 (TORC1).

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Epigenetics

Background:

  • Autophagy is essential for cellular homeostasis, differentiation, and development.
  • Regulation of autophagy by nutritional cues remains incompletely understood.
  • Chromatin remodeling and histone modifications play roles in cellular processes.

Purpose of the Study:

  • To elucidate the mechanism by which autophagy is regulated by nutrient availability.
  • To identify key proteins involved in the nutritional regulation of autophagy.
  • To uncover the role of chromatin remodeling in autophagy control.

Main Methods:

  • Biochemical assays to identify deacetylation targets.
  • Chromatin immunoprecipitation to assess protein-DNA interactions.
  • Genetic manipulation to study gene expression and autophagy induction.

Main Results:

  • The histone deacetylase Rpd3L complex targets chromatin remodeler Ino80 and histone variant H2A.Z for deacetylation.
  • Rpd3L-mediated deacetylation stabilizes Ino80, which then promotes H2A.Z eviction from autophagy-related genes.
  • Deacetylation of H2A.Z by Rpd3L further represses autophagy-related gene transcription.
  • The target of rapamycin complex 1 (TORC1) enhances Rpd3L activity; TORC1 inhibition induces autophagy.

Conclusions:

  • A novel mechanism involving Rpd3L, Ino80, and H2A.Z in the nutritional regulation of autophagy is described.
  • Chromatin remodeling and histone modifications are critical for modulating autophagy in response to nutrient availability.
  • This study provides insights into the interplay between epigenetic regulation and metabolic signaling in controlling autophagy.

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