Abstract

SummaryAutophagy is the degradation of cytoplasmic material through the lysosomal pathway. One of the most studied autophagy-related proteins is LC3. Despite growing evidence that LC3 is enriched in the nucleus, its nuclear role is poorly understood. Here, we show that Drosophila Atg8a protein, homologous to mammalian LC3, interacts with the transcription factor Sequoia in a LIR motif-dependent manner. We show that Sequoia depletion induces autophagy in nutrient-rich conditions through the enhanced expression of autophagy genes. We show that Atg8a interacts with YL-1, a component of a nuclear acetyltransferase complex, and that it is acetylated in nutrient-rich conditions. We also show that Atg8a interacts with the deacetylase Sir2, which deacetylates Atg8a during starvation to activate autophagy. Our results suggest a mechanism of regulation of the expression of autophagy genes by Atg8a, which is linked to its acetylation status and its interaction with Sequoia, YL-1, and Sir2.

Highlights

  • Autophagy is a fundamental, evolutionary conserved process in which cytoplasmic material is degraded through the lysosomal pathway

  • We show that Sequoia depletion induces autophagy in nutrient-rich conditions through the enhanced expression of autophagy genes

  • Our results suggest a novel mechanism of regulation of autophagy gene expression by Atg8a, which is linked to its acetylation status and its interaction with Sequoia, YL1, and Sir2

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Summary

Introduction

Evolutionary conserved process in which cytoplasmic material is degraded through the lysosomal pathway. It is a cellular response during nutrient starvation; yet, it is responsible in basal conditions for the removal of aggregated proteins and damaged organelles and plays an important role in the maintenance of cellular homeostasis (Ambrosio et al, 2019; Dikic and Elazar, 2018; Fu€llgrabe et al, 2014; Gatica et al, 2018; Lamb et al, 2013; Sakamaki et al, 2017, 2018). The products of degradation are transported back into the cytoplasm through lysosomal membrane permeases and can be reused by the cell (Dikic and Elazar, 2018; Gatica et al, 2018; Lamb et al, 2013)

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