Epigenetic Regulation of Autophagy Beyond the Cytoplasm: A Review.

Yin Shi,Han-Ming Shen,Nancy Gordon,Vidya Gopalakrishnan

doi:10.3389/fcell.2021.675599

Abstract

Autophagy is a highly conserved catabolic process induced under various stress conditions to protect the cell from harm and allow survival in the face of nutrient- or energy-deficient states. Regulation of autophagy is complex, as cells need to adapt to a continuously changing microenvironment. It is well recognized that the AMPK and mTOR signaling pathways are the main regulators of autophagy. However, various other signaling pathways have also been described to regulate the autophagic process. A better understanding of these complex autophagy regulatory mechanisms will allow the discovery of new potential therapeutic targets. Here, we present a brief overview of autophagy and its regulatory pathways with emphasis on the epigenetic control mechanisms.

Highlights

Macroautophagy, derived from a Greek term that refers to “selfeating,” is an evolutionary conserved and precisely regulated multi-step process that involves the engulfment of organelles and proteins into a double-membrane structure called the autophagosome, followed by fusion with a lysosome for degradation
Like transcription factor EB (TFEB), these transcription factors induce the expression of several genes responsible for autophagy induction and can be directly controlled by similar upstream signaling molecules involved in the regulation of cytoplasmic autophagy, such as AKT, mammalian target of rapamycin complex 1 (mTORC1), AMPK, and phosphatidylinositol 3-kinase (PI3K) (Seo et al, 2011; Calkin and Tontonoz, 2012, Webb and Brunet, 2014)
Despite the function of Sirtuin 1 (SIRT1) in deacetylation of light chain 3 (LC3) and induction of autophagy, AMPK-mediated SIRT1 activation leads to histone deacetylation and release of the epigenetic acetylation reader bromodomaincontaining protein 4 (BRD4) from the promoter regions of autophagy and lysosomal genes leading to transcriptional activation of autophagy

Summary

Introduction

Macroautophagy (hereafter called autophagy), derived from a Greek term that refers to “selfeating,” is an evolutionary conserved and precisely regulated multi-step process that involves the engulfment of organelles and proteins into a double-membrane structure called the autophagosome, followed by fusion with a lysosome for degradation. Like TFEB, these transcription factors induce the expression of several genes responsible for autophagy induction and can be directly controlled by similar upstream signaling molecules involved in the regulation of cytoplasmic autophagy, such as AKT, mTORC1, AMPK, and PI3K (Seo et al, 2011; Calkin and Tontonoz, 2012, Webb and Brunet, 2014).

Results

Conclusion