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Updated: Jul 24, 2025

Live Imaging Assay for Assessing the Roles of Ca2+ and Sphingomyelinase in the Repair of Pore-forming Toxin Wounds
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TECPR1 is activated by damage-induced sphingomyelin exposure to mediate noncanonical autophagy

Namrita Kaur1,2, Laura Rodriguez de la Ballina1,3, Håvard Styrkestad Haukaas1,2

  • 1Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway.

The EMBO Journal
|July 6, 2023
PubMed

Insights

TECPR1-containing E3 complexes are key mediators of noncanonical autophagy (CASM), labeling damaged cellular compartments. This process is activated by sphingomyelin exposure, independent of ATG16L1, revealing a new signaling pathway.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Noncanonical autophagy, or conjugation of ATG8 to single membranes (CASM), labels damaged cellular compartments to signal danger.
  • CASM utilizes E3 complexes to sense membrane damage, with only ATG16L1-containing complexes previously understood, linked to proton gradient loss.

Purpose of the Study:

  • To investigate the role of TECPR1-containing E3 complexes in CASM.
  • To elucidate the mechanism by which TECPR1 mediates CASM activation.

Main Methods:

  • Treatment of cells with various pharmacological agents, including nanoparticles, transfection reagents, and detergents.
  • Investigating TECPR1 activity in the presence of Salmonella Typhimurium pathogenicity factor SopF.
  • In vitro assays using purified human TECPR1-ATG5-ATG12 and ATG16L1-ATG5-ATG12 complexes.

Main Results:

  • TECPR1-containing E3 complexes are identified as key mediators of CASM across diverse cellular insults.
  • TECPR1 retains E3 activity even when ATG16L1 CASM activity is inhibited.
  • TECPR1 is recruited and activated by damage-induced sphingomyelin (SM) exposure, leading to ATG8 lipidation.
  • In vitro studies confirm direct activation of TECPR1 E3 activity by SM, while ATG16L1 E3 activity is unaffected by SM.

Conclusions:

  • TECPR1 is a crucial activator of CASM, functioning downstream of sphingomyelin exposure.
  • This discovery expands the understanding of CASM regulation and its response to cellular damage.
Keywords:
CASMDysFmembrane damagenoncanonical autophagysphingomyelin

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