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Dynamic regulation of macroautophagy by distinctive ubiquitin-like proteins

Nature Structural & Molecular Biology volume 21, pages 336–345 (2014)Cite this article

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Abstract

Autophagy complements the ubiquitin-proteasome system in mediating protein turnover. Whereas the proteasome degrades individual proteins modified with ubiquitin chains, autophagy degrades many proteins and organelles en masse. Macromolecules destined for autophagic degradation are 'selected' through sequestration within a specialized double-membrane compartment termed the phagophore, the precursor to an autophagosome, and then are hydrolyzed in a lysosome- or vacuole-dependent manner. Notably, a pair of distinctive ubiquitin-like proteins (UBLs), Atg8 and Atg12, regulate degradation by autophagy in unique ways by controlling autophagosome biogenesis and recruitment of specific cargos during selective autophagy. Here we review structural mechanisms underlying the functions and conjugation of these UBLs that are specialized to provide interaction platforms linked to phagophore membranes.

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Figure 1: Morphology of macroautophagy and location and functions of UBL Atg proteins.
Figure 2: Cargo recognition and packaging in selective macroautophagy.
Figure 3: Structural basis for Atg8-interacting motif (AIM) and LC3-interacting region (LIR) binding to ubiquitin-like protein Atg8 and orthologs.
Figure 4: Structural basis for Atg8 (LC3) processing and deconjugation.
Figure 5: Selected structures of autophagy UBL ligation enzymes.

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Acknowledgements

We thank S. Kaiser, M. Yamaguchi and Y. Qiu for helpful comments. The Klionsky laboratory is supported by US National Institutes of Health (NIH) grant 2R01GM053396. Research on autophagy in the Schulman laboratory is supported by the American Lebanese Syrian Associated Charities, the Howard Hughes Medical Institute, the St. Jude Cancer Center grant 5P30CA021765 and NIH grant R01GM077053.

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  1. klionsky@umich.edu

  2. brenda.schulman@stjude.org

Authors and Affiliations

  1. Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA

    Daniel J Klionsky & Daniel J Klionsky

  2. Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Brenda A Schulman & Brenda A Schulman

  3. Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Brenda A Schulman

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Klionsky, D., Schulman, B. Dynamic regulation of macroautophagy by distinctive ubiquitin-like proteins. Nat Struct Mol Biol 21, 336–345 (2014). https://doi.org/10.1038/nsmb.2787

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