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Updated: Jul 25, 2025

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

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An ATG12-ATG5-TECPR1 E3-like complex regulates unconventional LC3 lipidation at damaged lysosomes

Dale P Corkery1,2, Sergio Castro-Gonzalez1,2, Anastasia Knyazeva1,2

  • 1Department of Chemistry, Umeå University, Umeå, Sweden.

EMBO Reports
|June 29, 2023
PubMed

Insights

The study reveals TECPR1

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Lysosomal membrane damage threatens cell viability.
  • Cells possess repair (ESCRT) and clearance (lysophagy) mechanisms for damaged lysosomes.
  • The role of TECPR1 in lysosomal repair was previously unknown.

Purpose of the Study:

  • To investigate the function of TECPR1 in lysosomal membrane repair.
  • To elucidate the molecular mechanisms by which TECPR1 participates in lysosomal integrity maintenance.

Main Methods:

  • Investigated TECPR1 recruitment to damaged lysosomes.
  • Analyzed TECPR1's interaction with ESCRT and autophagy machinery.
  • Utilized ATG16L1/TECPR1 double knockout models to assess LC3 lipidation and lysosomal recovery.

Main Results:

  • Lysosomal damage triggers TECPR1 recruitment to damaged sites via its dysferlin domain.
  • TECPR1 acts upstream of galectin and lysophagy.
  • TECPR1 forms an E3-like complex with ATG12-ATG5, promoting ATG16L1-independent LC3 lipidation.
  • Impaired LC3 lipidation in TECPR1/ATG16L1 double knockouts hinders lysosomal repair.

Conclusions:

  • TECPR1 plays a novel, crucial role in lysosomal membrane repair.
  • TECPR1 facilitates an unconventional LC3 lipidation pathway essential for lysosomal recovery.
  • This finding expands our understanding of cellular damage response and autophagy regulation.
Keywords:
TECPR1autophagylysophagylysosomemembrane repair

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