Atg101: Not Just an Accessory Subunit in the Autophagy-initiation Complex

Abstract

ABSTRACT. The Saccharomyces cerevisiae autophagy-initiation complex, Atg1 kinase complex, consists of Atg1, Atg13, Atg17, Atg29, and Atg31, while the corresponding complex in most other eukaryotes, including mammals, is composed of ULK1 (or ULK2), Atg13, FIP200 (also known as RB1CC1), and Atg101. ULKs are homologs of Atg1, and FIP200 is partially homologous to Atg17. However, the sequence of Atg101 is not similar to that of Atg29 or Atg31. Although Atg101 is essential for autophagy and widely conserved in eukaryotes, its precise function and structure have remained largely unknown. Now, structural and cell biological analysis of Atg101 together with its binding partner Atg13 reveal that Atg101 is required for stabilization of "uncapped" Atg13 in most eukaryotes and also for recruitment of downstream Atg proteins through the newly identified WF motif. By contrast, S. cerevisiae has stable "capped" Atg13, which does not require Atg101 for its stabilization. Possible roles for other binding partners such as Atg29, Atg31, and Atg28 in different organisms are also discussed.

The exponential growth of autophagy‐related research: from the humble yeast to the Nobel Prize

“…For example, subunits of the autophagy-initiation complex are different among organisms. The latter consists of Atg1, Atg13, Atg17, Atg29, and Atg31 in S. cerevisiae; Atg1, Atg13, Atg17, and Atg28 in Pichia pastoris; or ULK, ATG13, RB1CC1 (also known as FIP200), and ATG101 in mammals [32]. This difference suggests that autophagy regulation may differ among these organisms.…”

Liquid–liquid phase separation in autophagy

“…In multicellular organisms, the ULK1 complex contains ATG13, which possesses abundant IDRs and is phosphoregulated by mTORC1, similar to yeast Atg13, although the ULK1 complex forms constitutively (Noda and Fujioka, 2015;Noda and Mizushima, 2016). ATG proteins are recruited to the autophagosome formation sites in a hierarchical manner, which is in principle similar to the PAS recruitment of ATG proteins in yeast (Fig.…”

Structural Biology and Electron Microscopy of the Autophagy Molecular Machinery

“…Like ATG1, orthologs of ATG13 have been found in a number of angiosperms. The yeast scaffolding protein Atg17 is predicted to function as FIP200 in mammals [95], but the budding yeast Saccharomyces cerevisiae possesses no Atg101 and its Atg1 complex subunits Atg29 and Atg31 have no orthologs in mammals [96,97]. In Arabidopsis, ATG17 and ATG101 have been identified, but how they function as regulatory and/or scaffolding subunits is largely unknown and awaits future investigation [98].…”