A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy

Macroautophagy is an intracellular, vesicle-mediated mechanism for the sequestration and ultimate lysosomal degradation of cytoplasmic proteins, organelles and macromolecules.  The macroautophagy process and many of the autophagy specific (Atg) proteins are remarkably well conserved in higher eukaryotes.  In yeast, the Atg1 kinase complex includes Atg1, Atg13, Atg17, and at least four other interacting proteins, some of which are phosphorylated in a TOR-dependent manner, placing the Atg1 signaling complex downstream of a major nutrient-sensing pathway.  Atg1 orthologs, including mammalian unc-51-like kinase 1 (ULK1), have been identified in higher eukaryotes and have been functionally linked to autophagy.  This suggests that other components of the Atg1 complex exist in higher eukaryotes.  Recently, a putative human Atg13 ortholog, FLJ20698, was identified by gapped-BLAST analysis.  We show here that FLJ20698 (Atg13) is a ULK1-interacting phosphoprotein that is essential for macroautophagy.  Furthermore, ...