Autophagy signal transduction by ATG proteins: from hierarchies to networks.

Sebastian Wesselborg,Björn Stork

doi:10.1007/s00018-015-2034-8

Sebastian Wesselborg, Björn Stork

Open Access

https://doi.org/10.1007/s00018-015-2034-8

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Abstract

Autophagy represents an intracellular degradation process which is involved in both cellular homeostasis and disease settings. In the last two decades, the molecular machinery governing this process has been characterized in detail. To date, several key factors regulating this intracellular degradation process have been identified. The so-called autophagy-related (ATG) genes and proteins are central to this process. However, several additional molecules contribute to the outcome of an autophagic response. Several review articles describing the molecular process of autophagy have been published in the recent past. In this review article we would like to add the most recent findings to this knowledge, and to give an overview of the network character of the autophagy signaling machinery.Electronic supplementary materialThe online version of this article (doi:10.1007/s00018-015-2034-8) contains supplementary material, which is available to authorized users.

Highlights

The term autophagy originates from the Greek expressions auso1 and uaceım, literally meaning the self-eating of a cell
In contrast to the results described above, the binding site of ATG13–ATG101 within ULK1 was mapped to the N-terminal half of the PS-rich domain, proximal to the kinase domain [38]
The molecular understanding of this process has been initiated by the identification of Atg/ATG proteins, and at present the network character of this signaling machinery and the identification of scaffolding/signaling platforms are shifting into focus

Summary

Introduction

Mammalian ATGs can be subdivided in six functional clusters (Fig. 1): (1) the ULK1–ATG13– FIP200–ATG101 protein kinase complex; (2) the PtdIns3K class III complex containing the core proteins VPS34, VPS15 and Beclin 1; (3) the PtdIns3P-binding WIPI/ ATG18–ATG2 complex; (4) the multi-spanning transmembrane protein ATG9A; (5) the ubiquitin-like ATG5/ ATG12 system and (6) the ubiquitin-like ATG8/LC3 conjugation system (reviewed in [8]) These six modules regulate different steps during autophagosome biogenesis, i.e., vesicle nucleation, elongation of the autophagosomal membrane, and autophagosome completion. The authors confirmed that binding of Atg to Atg promotes its kinase activity and is important for efficient autophagy in vivo, the described observation would suggest that Atg activation in yeast is not exclusively controlled by regulated Atg binding, but rather involves additional levels of control. DT40 B cells Release from ULK1–Hsp90–Cdc complex; recruitment to damaged mitochondria ND ND Increased activity of ATG14-containing VPS34 complex ND Activation of myosin light chain kinase and activation of myosin II; regulation of Atg trafficking

Conclusion

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