bims-nocaut Biomed News
on Non-canonical autophagy
Issue of 2025–11–16
two papers selected by
Quentin Frenger, University of Strasbourg
  1. Autophagosome marker, LC3, is released extracellularly via several distinct pathways.
  2. Endosomal microautophagy is activated by specific cellular stresses in trout hepatocytes.
  1. FEBS Open Bio. 2025 Nov 10.
    Autophagosome marker, LC3, is released extracellularly via several distinct pathways.
    Koki Saito, Masashi Arakawa, Koki Maeda, Eiji Morita.
      Autophagy-mediated secretion contributes to the maintenance of intracellular homeostasis by releasing cytoplasmic components into the extracellular space. However, several aspects of the process remain unclear. In this study, we developed an ultrasensitive detection system using HiBiT tag/NanoBiT technology to analyze the conditions that trigger the secretion of LC3, an autophagosome marker. In HiBiT-tagged knock-in cells, a detectable amount of HiBiT-dependent NanoLuc luciferase activity (HiBiT activity) from HiBiT-fused LC3 was observed in the culture supernatants. However, the levels were lower than those of CD63. HiBiT activity was detected only in the presence of detergent, indicating that LC3 was released from the lipid membranes. Treatment with bafilomycin A1 significantly increased the extracellular HiBiT activity, which was diminished in ATG5 or FIP200 knockout cells, suggesting that this release depends on autophagosome formation. However, some HiBiT-LC3 was detected in these knockout cells, indicating that LC3 may be released via an autophagy-independent mechanism. The introduction of a C-terminal truncation (ΔG) or the K51A/L53A mutation also reduced LC3 release, but did not completely inhibit it, suggesting that multiple pathways exist for LC3 release. This system is expected to elucidate the mechanisms underlying autophagy-mediated secretion.
    Keywords:  HiBiT tag; LC3 family; autophagic secretion; autophagy; knock‐in cells; lysosome
    DOI:  https://doi.org/10.1002/2211-5463.70150
  2. Sci Rep. 2025 Nov 10. 15(1): 39347
    Endosomal microautophagy is activated by specific cellular stresses in trout hepatocytes.
    Emilio J Vélez, Vincent Véron, Jeanne Gouis, Steffi Reji, Karine Dias, Amaury Herpin, Florian Beaumatin, Iban Seiliez.
      Endosomal microautophagy (eMI) is a recently discovered autophagic process where cytosolic proteins are selectively captured in late endosome/multivesicular bodies (LE/MVB). This pathway, similar to chaperone-mediated autophagy (CMA), involves the recognition of KFERQ-like motif containing proteins by HSC70. While CMA targets substrates to lysosomes via the receptor LAMP2A, eMI involves internalization into intraluminal vesicles within LE/MVB through interactions with ESCRT machinery. Although the same proteins could be targeted by either pathway, eMI's role in cellular homeostasis is less understood. Our research identified an eMI-like process in rainbow trout hepatocytes, triggered by oxidative stress, high-glucose, DNA damage, and nutrient deprivation, but not serum deprivation. This finding suggests eMI's stimulus-specific induction and its potential compensatory role when CMA is impaired. Our study provides new insights into eMI and offers novel model organisms for exploring its interactions with CMA, enhancing our understanding of cellular stress responses.
    DOI:  https://doi.org/10.1038/s41598-025-23022-x
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