Receptor protein complexes are in control of autophagy

Abstract

In autophagic processes a variety of cargos is delivered to the degradative compartment of cells. Recent progress in autophagy research has provided support for the notion that when autophagic processes are operating in selective mode, a receptor protein complex will process the cargo. Here we present a concept of receptor protein complexes as comprising a functional tetrad of components: a ligand, a receptor, a scaffold and an Atg8 family protein. Our current understanding of each of the four components and their interaction in the context of cargo selection are considered in turn.

Keywords: Atg8 family protein; autophagic cargo; ligand; phagophore; receptor; scaffold protein.

Figure 1. Receptor protein complexes in macroautophagy. (A) A general model of the receptor protein complex. (B) The Cvt pathway (left) and mitophagy (right) in yeast with their respective cargos (prApe1 complex, mitochondrion), ligand (prApe1 propeptide), receptors (Atg19 and Atg32), scaffold (Atg11) and Atg8 family protein (Atg8). (C) Aggrephagy (left) and mitophagy (right) in mammalian cells and their receptor protein complexes. BNIP3L might act as a “mammalian Atg32” being integral to the mitochondrial outer membrane and interacting with LC3. SQSTM1 binds to ubiquitin (Ub) conjugated to aggregated proteins and mediates their interaction with the autophagic scaffold (WDFY3) and Atg8 family protein (LC3); SQSTM1 might play a similar role during pexophagy, mitophagy and xenophagy. Note that SQSTM1 might also directly recognize several ligands for aggrephagy and xenophagy in a Ub-independent manner (Table 1).