Many roads lead to CASM: Diverse stimuli of noncanonical autophagy share a unifying molecular mechanism

Joanne Durgan1, Oliver Florey1

  • 1Babraham Institute, Signalling Program, Cambridge, UK.

Science Advances
|October 26, 2022
PubMed

Insights

Autophagy-related proteins coordinate canonical and noncanonical autophagy, a signaling pathway crucial for immunity and disease. This review unifies mechanisms of noncanonical autophagy, focusing on ATG16L1 and V-ATPase.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Autophagy is a fundamental catabolic process.
  • Autophagy-related (ATG) proteins coordinate this process.
  • ATG proteins also regulate noncanonical autophagy, a lysosome-associated signaling pathway.

Purpose of the Study:

  • To review stimuli and processes utilizing noncanonical autophagy.
  • To discuss conjugation of ATG8 to single membranes (CASM) routes.
  • To propose an updated, unifying mechanism for noncanonical autophagy.

Main Methods:

  • Literature review of stimuli and processes.
  • Analysis of CASM routes and molecular features.
  • Integration of findings to propose a unifying mechanism.

Main Results:

  • Noncanonical autophagy involves diverse stimuli like drug treatments, viral infections, and signaling pathways (TRPML1, STING).
  • Multiple routes lead to CASM, sharing and distinct molecular features.
  • An updated mechanism for noncanonical autophagy is proposed, centered on ATG16L1 and V-ATPase.

Conclusions:

  • Noncanonical autophagy, while sharing ATG machinery, has distinct mechanisms and functions.
  • ATG16L1 and V-ATPase are central to a unifying model of noncanonical autophagy.
  • Understanding noncanonical autophagy is vital for immunity, inflammation, cancer, and neurodegeneration research.

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