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Abstract
During the past 20 years, autophagy signaling has entered the main stage of the cell biological theater. Autophagy represents an intracellular degradation process that is involved in both the bulk recycling of cytoplasmic components and the selective removal of organelles, protein aggregates, or intracellular pathogens. The understanding of autophagy has been greatly facilitated by the characterization of the molecular machinery governing this process. In yeast, initiation of autophagy is controlled by the Atg1 kinase complex, which is composed of the Ser/Thr kinase Atg1, the adaptor protein Atg13, and the ternary complex of Atg17-Atg31-Atg29. In vertebrates, the orthologous ULK1 kinase complex contains the Ser/Thr kinase ULK1 and the accessory proteins ATG13, RB1CC1, and ATG101. Among these components, Atg1/ULK1 have gained major attention in the past, i.e., for the identification of upstream regulatory kinases, the characterization of downstream substrates controlling the autophagic flux, or as a druggable target for the modulation of autophagy. However, accumulating data indicate that the function of Atg13/ATG13 has been likely underestimated so far. In addition to ensuring proper Atg1/ULK1 recruitment and activity, this adaptor molecule has been implicated in ULK1-independent autophagy processes. Furthermore, recent data have identified additional binding partners of Atg13/ATG13 besides the components of the Atg1/ULK1 complex, e.g., Atg8 family proteins or acidic phospholipids. Therefore, in this review we will center the spotlight on Atg13/ATG13 and summarize the role that Atg13/ATG13 assumes in the autophagy stage play.
Disclosure of Potential Conflict of Interest
The authors declare no conflict of interest.
Acknowledgments
Related research of BS is supported by grants from the Deutsche Forschungsgemeinschaft (STO 864/3-1) and from the Research Committee of the Medical Faculty of the Heinrich-Heine-University Düsseldorf (58/2013).
Note Added in Proof
During preparation/publication of this review article, Fujioka et al. reported the X-ray crystallographic analysis of the interaction of yeast Atg13 with Atg1 and Atg17 (Nat Struct Mol Biol 2014 May 4. 10.1038/nsmb.2822). Atg13 binds tandem microtubule interacting and transport (tMIT) domains in Atg1 via a 2-part MIT interacting motif (residues 460–521). The authors suggest that this mode of interaction is conserved in mammals. Additionally, the Atg17-binding region was mapped to amino acids 424–436 of Atg13. Finally, the authors propose that starvation-induced dephosphorylation of specific serine residues in Atg13 enhances the interaction with both Atg1 and Atg17.