One step closer to understanding mammalian macroautophagy initiation: Interplay of 2 HORMA architectures in the ULK1 complex.

ULK1 and ATG13 assemble with RB1CC1/FIP200 and ATG101 to form a macroautophagy (hereafter autophagy) induction (ULK1) complex in higher eukaryotes. The yeast counterpart, the Atg1 complex, is comprised of Atg1 and Atg13 (ULK1 and ATG13 homologs), Atg17 (a proposed functional homolog of RB1CC1), and either the Atg101 subunit (in Schizosaccharomyces pombe) or the Atg29-Atg31 heterodimer (in Saccharomyces cerevisiae). With mutual exclusivity of, and no detectable homology between, the Atg29-Atg31 dimer and Atg101, knowledge about the roles of these proteins in autophagy induction is an important piece in the puzzle of understanding the molecular mechanism of autophagy initiation. A recent study reporting the structure of the S. pombe homolog Atg101 bound to the Atg13HORMA domain is a notable contribution to this knowledge (see the punctum in this issue of the journal).