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Updated: Nov 7, 2025
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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
Published on: January 31, 2025
791
TFG binds LC3C to regulate ULK1 localization and autophagosome formation
Marianna Carinci1,2, Beatrice Testa3, Matteo Bordi1,3
1Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
The EMBO Journal
|May 1, 2021
Summary
The Trk-fused gene (TFG) protein is crucial for autophagy, impacting autophagosome formation by linking the early secretory pathway to this essential cellular process. Mutations in TFG impair autophagy, highlighting its role in cellular health.
Area of Science:
- Cell Biology
- Molecular Biology
- Endomembrane System Dynamics
Background:
- The early secretory pathway and autophagy are vital endomembrane processes with interconnected roles.
- The precise molecular mechanisms governing autophagosome biogenesis via intracellular trafficking are not fully elucidated.
Purpose of the Study:
- To investigate the role of the COPII vesicle-related protein TFG in autophagy induction and autophagosome formation.
- To define the molecular interactions and regulatory network involving TFG in autophagy.
Main Methods:
- Assessed the impact of TFG on ULK1 puncta formation and localization during autophagy.
- Analyzed the dynamics of LC3B association with early ATG proteins.
- Examined autophagy and ULK1 puncta accumulation in fibroblasts from HSP patients with mutated TFG.
- Investigated the interaction between TFG, LC3C, and ULK1 using LIR motif analysis.
Main Results:
- TFG significantly influences ULK1 puncta number and localization, affecting isolation membrane formation.
- Proper dynamics of LC3B and early ATG proteins, as well as omegasome and autophagosome formation, depend on TFG.
- Hereditary spastic paraplegia patient fibroblasts with mutated TFG exhibit autophagy defects.
- TFG's autophagic activity is mediated by its interaction with LC3C via a LIR motif, promoting LC3C-ULK1 binding.
Conclusions:
- TFG acts as a molecular scaffold connecting the early secretory pathway with autophagy.
- TFG is essential for proper autophagosome biogenesis and cellular homeostasis.
- Defects in TFG function contribute to autophagy-related disorders like hereditary spastic paraplegia.
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