Dynamic regulation of macroautophagy by distinctive ubiquitin-like proteins

Nat Struct Mol Biol. 2014 Apr;21(4):336-45. doi: 10.1038/nsmb.2787.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adaptor Proteins, Signal Transducing / physiology
  • Autophagy / physiology*
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Cysteine Endopeptidases / metabolism
  • Cysteine Endopeptidases / physiology
  • Humans
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism
  • Microfilament Proteins / physiology
  • Models, Biological
  • Proteasome Endopeptidase Complex / physiology
  • Proteolysis
  • Ubiquitins / chemistry
  • Ubiquitins / metabolism
  • Ubiquitins / physiology*


  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • GABARAPL2 protein, human
  • Microfilament Proteins
  • Ubiquitins
  • ATG4A protein, human
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex