The role of the HORMA domain proteins ATG13 and ATG101 in initiating autophagosome biogenesis

Abstract

Autophagy is a process of regulated degradation. It eliminates damaged and unnecessary cellular components by engulfing them with a de novo‐generated organelle: the double‐membrane autophagosome. The last three decades have provided us with a detailed parts list of the autophagy initiation machinery, have developed important insights into how these processes function and have identified regulatory proteins. It is now clear that autophagosome biogenesis requires the timely assembly of a complex machinery. However, it is unclear how a putative stable machine is assembled and disassembled, and how the different parts cooperate to perform its overall function. Although they have long been somewhat enigmatic in their precise role, HORMA domain proteins (first identified in Hop1p, Rev7p and MAD2 proteins) autophagy‐related protein 13 (ATG13) and ATG101 of the ULK‐kinase complex have emerged as important coordinators of the autophagy‐initiating subcomplexes. Here, we will particularly focus on ATG13 and ATG101 and the role of their unusual metamorphosis in initiating autophagosome biogenesis. We will also explore how this metamorphosis could potentially be purposefully rate‐limiting and speculate on how it could regulate the spontaneous self‐assembly of the autophagy‐initiating machinery.

Dynamic monitoring of TGW6 by selective autophagy during grain development in rice

“…Out of the rest OsATGs , we selected OsATG13a , encoding a putative autophagy induction component, and OsATG9b , encoding a putative autophagosome biogenesis component, as representatives to dissect the role of autophagy in regulating agronomic traits in rice since they are supposed to function in the key steps of autophagic machinery (induction of autophagy and formation of autophagosome, respectively; Marshall & Vierstra, 2018). ATG13 is a scaffold protein in ATG1 kinase complex, and its phosphorylation status‐regulated phase separation controls the initiation of autophagy (Fujioka et al ., 2020; Qi et al ., 2022; Nguyen & Faesen, 2023). ATG9 is a scramblase that regulates phagophore expansion (Chumpen Ramirez et al ., 2023; Olivas et al ., 2023).…”

Autophagy—from yeast to humans: Thirty years of molecular autophagy

“…This review article demonstrates the molecular detail with which current autophagy research provides important insights into the specific functions of the individual parts of the autophagy machinery. Moreover, a detailed insight into the regulation of the initiation complex for autophagosome biogenesis is provided by describing the metamorphosis of the HORMA domain proteins ATG13 and ATG101 in the review by Nguyen and Faesen [29].…”