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Atg7-Atg12 conjugation and autophagy are negatively regulated by the disordered region of Atg12

Hana Popelka1, Daniel J Klionsky2,3

  • 1Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA. popelka@umich.edu.

Communications Biology
|May 15, 2026
PubMed

Insights

Autophagy utilizes two ubiquitin-like (UBL) conjugation systems. Specific N-termini on Atg8 and Atg12 proteins dictate their conjugation to Atg7, controlling autophagy levels.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Autophagy involves two ubiquitin-like (UBL) conjugation systems: Atg8 and Atg12.
  • Atg7, a non-canonical E1 enzyme, conjugates both Atg8 and Atg12.
  • Differential conjugation efficiency of Atg8 and Atg12 by Atg7 remains unclear.

Purpose of the Study:

  • Investigate the molecular mechanisms by which Atg7 distinguishes between Atg8 and Atg12.
  • Elucidate the role of protein N-termini in selective UBL conjugation during autophagy.

Main Methods:

  • Analysis of recombinant yeast protein complexes.
  • Biochemical assays to study protein conjugation.

Main Results:

  • The N-termini of Atg8 and Atg12 are critical determinants for their conjugation to Atg7.
  • Atg12's disordered N-terminus negatively regulates its conjugation to Atg7 and autophagy.
  • Atg8's N-terminal helical domain promotes autophagy and enhances binding to Atg7.
  • N-termini direct selective transfer of UBLs to cognate E2 enzymes (Atg3 and Atg10).

Conclusions:

  • Distinct N-terminal structures of Atg8 and Atg12 are essential for differential conjugation by Atg7.
  • These structural differences regulate the balance of the two UBL conjugation systems in autophagy.
  • Findings advance the understanding of the complex autophagy machinery.

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