Cellular cleanup process ramps up under stress, study finds

Jenn Hoskins
15th November, 2025

Cellular cleanup process ramps up under stress, study finds

Mild oxidative stress triggers a cellular process called endosomal microautophagy (eMI) in rainbow trout cells, leading to the accumulation of a fluorescent signal within compartments of the cell responsible for breaking down proteins.

Image adapted from: Vélez et al. / CC BY (Source)

Key Findings

  • This study, conducted on rainbow trout liver cells, identified a cellular ‘self-eating’ process called endosomal microautophagy (eMI)
  • eMI is triggered by various stressors like oxidative damage, high glucose, DNA damage, and nutrient loss, but not by simple starvation
  • eMI functions as a backup system when another similar process, chaperone-mediated autophagy (CMA), is impaired, helping maintain cell health
Cells constantly need to break down and recycle components to stay healthy. One key process for this is autophagy – essentially a cellular ‘self-eating’ mechanism[2]. Several types of autophagy exist, each with a slightly different method for delivering unwanted materials to cellular recycling centers called lysosomes. One well-studied form is chaperone-mediated autophagy (CMA), where specific proteins are directly transported to lysosomes[3][4]. More recently, a related process called endosomal microautophagy (eMI) has been discovered, where proteins are captured within compartments called late endosomes/multivesicular bodies (LE/MVBs) before being degraded[5]. While both CMA and eMI rely on the chaperone protein HSC70 to identify proteins for breakdown, they differ in how they deliver those proteins to be recycled. Understanding these differences, and how they respond to cellular stress, is crucial for understanding overall cell health. Researchers at INRAE & Université de Pau et des Pays de l’Adour recently investigated eMI in liver cells from rainbow trout, aiming to understand what triggers this process and how it compares to CMA[1]. They found that eMI is activated by several different types of stress – oxidative stress (damage from unstable molecules), high glucose levels, DNA damage, and nutrient deprivation. Interestingly, it wasn’t activated by serum deprivation, a condition often used to stimulate CMA. This suggests that eMI and CMA aren’t simply interchangeable; they respond to different signals. The discovery builds on earlier work showing that eMI involves the selective capture of proteins containing a specific sequence (KFERQ-like motif) by HSC70[5]. This is similar to CMA, where HSC70 also plays a role in identifying proteins destined for lysosomes[3]. However, while CMA relies on a receptor protein called LAMP-2A to transport proteins directly to the lysosome[4], eMI uses a different mechanism. It involves packaging the captured proteins into small vesicles within the LE/MVB, utilizing a cellular machinery called ESCRT. This ESCRT system is also involved in forming MVBs, suggesting a close link between eMI and the normal process of creating these compartments[5]. The study’s findings suggest that eMI might act as a backup system when CMA is impaired. By responding to different stress signals, eMI could help maintain cellular protein balance even if CMA isn’t functioning optimally. This is particularly relevant because both CMA and eMI are thought to be important in preventing the buildup of toxic protein aggregates, which are hallmarks of neurodegenerative diseases[2]. The researchers’ use of rainbow trout liver cells as a model system is also significant. While much autophagy research is done in human cells, using different organisms can reveal new insights and potentially simplify the study of complex cellular processes. The trout cells provided a robust system for studying eMI, and the findings could be relevant to understanding autophagy in other species, including humans. The study expands on the understanding of microautophagy, a process that was previously less well understood than macroautophagy and CMA[2].

GeneticsBiochemAnimal Science

References

Main Study

1) Endosomal microautophagy is activated by specific cellular stresses in trout hepatocytes

Published 10th November, 2025

https://doi.org/10.1038/s41598-025-23022-x

Related Studies

2) The emerging mechanisms and functions of microautophagy.

https://doi.org/10.1038/s41580-022-00529-z

3) A molecular chaperone complex at the lysosomal membrane is required for protein translocation.

Journal: Journal of cell science, Issue: Vol 114, Issue Pt 13, Jul 2001

4) The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane.

https://doi.org/10.1128/MCB.02070-07

5) Microautophagy of cytosolic proteins by late endosomes.

https://doi.org/10.1016/j.devcel.2010.12.003


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