Autophagy: machinery and regulation - PubMed (original) (raw)

Review

Autophagy: machinery and regulation

Zhangyuan Yin et al. Microb Cell. 2016.

Abstract

Macroautophagy/autophagy is an evolutionarily conserved cellular degradation process that targets cytoplasmic materials including cytosol, macromolecules and unwanted organelles. The discovery and analysis of autophagy-related (Atg) proteins have unveiled much of the machinery of autophagosome formation. Although initially autophagy was regarded as a survival response to stress, recent studies have revealed its significance in cellular and organismal homeostasis, development and immunity. Autophagic dysfunction and dysregulation are implicated in various diseases. In this review, we briefly summarize the physiological roles, molecular mechanism, regulatory network, and pathophysiological roles of autophagy.

Keywords: autophagosome formation; autophagy; cellular homeostasis; pathogenesis; physiological roles; regulation.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: The authors declare no conflict of interest.

Figures

Figure 1

Figure 1. Figure 1: the mechanistic features of yeast autophagy.

Initiation of autophagy requires the formation of the Atg1 kinase complex at the PAS to allow the recruitment and activation of other Atg proteins. In yeast there is typically one PAS per cell, but the precise nature of this site is not well defined; the PAS may literally become a phagophore, making it a dynamic structure that continuously reforms. Next, the PtdIns3K complex translocates to the PAS to begin the nucleation process that will catalyze further movement of additional Atg proteins to this site. Ubl proteins such as Atg8–PE participate in cargo recognition during selective types of autophagy, and also play a role in determining the size of the autophagosome. Membrane delivery to the phagophore allows expansion and maturation into an autophagosome. This process also employs the transmembrane protein Atg9; however, the mechanism for phagophore expansion is poorly understood. Upon autophagosome completion, Atg4 deconjugates Atg8–PE on the surface of the autophagosome and the resulting vesicle fuses with the vacuole. In yeast, the inner vesicle is released into the lumen as an autophagic body. Within the vacuole, the contents of the autophagic body are released following lysis by the putative lipase Atg15. Finally, the cargo is degraded by resident hydrolases, and the resulting macromolecules are then released back into the cytosol via permeases.

Similar articles

Cited by

References

    1. Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science. 2000;290(5497):1717–1721. doi: 10.1126/science.290.5497.1717. - DOI - PMC - PubMed
    1. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal. 2014;20(3):460–473. doi: 10.1089/ars.2013.5371. - DOI - PMC - PubMed
    1. Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy. 2011;7(3):279–296. doi: 10.4161/auto.7.3.14487. - DOI - PMC - PubMed
    1. Mijaljica D, Nazarko TY, Brumell JH, Huang W-P, Komatsu M, Prescott M, Simonsen A, Yamamoto A, Zhang H, Klionsky DJ, Devenish RJ. Receptor protein complexes are in control of autophagy. Autophagy. 2012;8(11):1701–1705. doi: 10.4161/auto.21332. - DOI - PMC - PubMed
    1. Okamoto K. Organellophagy: eliminating cellular building blocks via selective autophagy. J Cell Biol. 2014;205(4):435–445. doi: 10.1083/jcb.201402054. - DOI - PMC - PubMed

Publication types

Grants and funding

This work was supported by NIH grant GM053396 to DJK.

LinkOut - more resources