ATG5: A central autophagy regulator implicated in various human diseases

Cell Biochem Funct. 2022 Oct;40(7):650-667. doi: 10.1002/cbf.3740. Epub 2022 Sep 5.

Abstract

Autophagy, an intracellular conserved degradative process, plays a central role in the renewal/recycling of a cell to maintain the homeostasis of nutrients and energy within the cell. ATG5, a key component of autophagy, regulates the formation of the autophagosome, a hallmark of autophagy. ATG5 binds with ATG12 and ATG16L1 resulting in E3 like ligase complex, which is necessary for autophagosome expansion. Available data suggest that ATG5 is indispensable for autophagy and has an imperative role in several essential biological processes. Moreover, ATG5 has also been demonstrated to possess autophagy-independent functions that magnify its significance and therapeutic potential. ATG5 interacts with various molecules for the execution of different processes implicated during physiological and pathological conditions. Furthermore, ATG5 genetic variants are associated with various ailments. This review discusses various autophagy-dependent and autophagy-independent roles of ATG5, highlights its various deleterious genetic variants reported until now, and various studies supporting it as a potential drug target.

Keywords: ATG12-ATG5/ATG16L1; ATG5; ATG5 polymorphism; autophagosome; autophagy.

Publication types

  • Review

MeSH terms

  • Autophagy*
  • Autophagy-Related Protein 12 / genetics
  • Autophagy-Related Protein 12 / metabolism
  • Autophagy-Related Protein 5 / genetics
  • Autophagy-Related Protein 5 / metabolism
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Humans
  • Ligases
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 5
  • Autophagy-Related Proteins
  • Microtubule-Associated Proteins
  • Ligases