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. 2013 Mar;9(3):424-5.
doi: 10.4161/auto.22931. Epub 2013 Jan 15.

Dissecting the role of the Atg12-Atg5-Atg16 complex during autophagosome formation

Marta Walczak  1 , Sascha Martens
Affiliations

Dissecting the role of the Atg12-Atg5-Atg16 complex during autophagosome formation

Marta Walczak et al. Autophagy. 2013 Mar.

Abstract

The activity of the conserved Atg12-Atg5-Atg16 complex is essential for autophagosome formation. However, little is known about its mechanism of action during this process. In our study we employed in vitro systems consisting of purified proteins and giant unilamellar vesicles (GUVs) or small liposomes to investigate membrane binding by the Atg12-Atg5-Atg16 complex and its interplay with the Atg8 conjugation system. We showed that Atg5 directly binds membranes and that this membrane binding is negatively regulated by Atg12 conjugation but activated by Atg16. Membrane binding by the Atg12-Atg5-Atg16 complex is required for efficient promotion of Atg8 lipidation. Additionally, we found that the Atg12-Atg5-Atg16 complex tethered vesicles in an Atg8-independent manner. In yeast, membrane binding by Atg5 is not required for its recruitment to the phagophore assembly site (PAS) but is essential for efficient promotion of autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway at a stage preceding Atg8 lipidation and autophagosome closure. Our findings provide new insights into the role of the Atg12-Atg5-Atg16 complex during autophagosome formation.

Keywords: Atg12; Atg16; Atg5; Atg8; autophagosome; cytoplasm-to-vacuole targeting; phagophore assembly site.

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Figures

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Figure 1. Potential roles of the Atg12–Atg5-Atg16 complex during autophagosome formation. The association of the Atg12–Atg5 conjugate with Atg16 unmasks a membrane-binding site in Atg5 and allows it to bind to phagophore precursors. Due to the dimerization of Atg16, each molecule of the Atg12–Atg5-Atg16 complex contains two molecules of Atg5 enabling Atg12–Atg5-Atg16 to tether vesicles. Atg12 stimulates this tethering activity. In addition, Atg16-dependent membrane localization of Atg12 is required to bring Atg8-bound Atg3 to the membrane. This in turn facilitates the conjugation of Atg8 to PE.
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Comment on

  • Romanov J, Walczak M, Ibiricu I, Schüchner S, Ogris E, Kraft C, et al. Mechanism and functions of membrane binding by the Atg5-Atg12/Atg16 complex during autophagosome formation. EMBO J. 2012;31:4304–17. doi: 10.1038/emboj.2012.278.

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