The Atg8 family: multifunctional ubiquitin-like key regulators of autophagy

Essays Biochem. 2013;55:51-64. doi: 10.1042/bse0550051.

Abstract

Autophagy is an evolutionarily-conserved catabolic process initiated by the engulfment of cytosolic components in a crescent-shaped structure, called the phagophore, that expands and fuses to form a closed double-membrane vesicle, the autophagosome. Autophagosomes are subsequently targeted to the lysosome/vacuole with which they fuse to degrade their content. The formation of the autophagosome is carried out by a set of autophagy-related proteins (Atg), highly conserved from yeast to mammals. The Atg8s are Ubl (ubiquitin-like) proteins that play an essential role in autophagosome biogenesis. This family of proteins comprises a single member in yeast and several mammalian homologues grouped into three subfamilies: LC3 (light-chain 3), GABARAP (γ-aminobutyric acid receptor-associated protein) and GATE-16 (Golgi-associated ATPase enhancer of 16 kDa). The Atg8s are synthesized as cytosolic precursors, but can undergo a series of post-translational modifications leading to their tight association with autophagosomal structures following autophagy induction. Owing to this feature, the Atg8 proteins have been widely served as key molecules to monitor autophagosomes and autophagic activity. Studies in both yeast and mammalian systems have demonstrated that Atg8s play a dual role in the autophagosome formation process, coupling between selective incorporation of autophagy cargo and promoting autophagosome membrane expansion and closure. The membrane-remodelling activity of the Atg8 proteins is associated with their capacity to promote tethering and hemifusion of liposomes in vitro.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Autophagy*
  • Cytoplasmic Vesicles / metabolism
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Microtubule-Associated Proteins
  • Ubiquitins