# Endosomal microautophagy is activated by specific cellular stresses in trout hepatocytes

## TL;DR

This study shows that trout liver cells activate a specific type of cell cleanup called endosomal microautophagy in response to various stresses like high glucose or DNA damage.

## Contribution

The study identifies a stress-specific activation of endosomal microautophagy in trout hepatocytes and its potential compensatory role when another cleanup pathway is impaired.

## Key findings

- Endosomal microautophagy is activated in trout hepatocytes under oxidative stress, high-glucose, DNA damage, and nutrient deprivation.
- The process is not triggered by serum deprivation, indicating stimulus specificity.
- The findings suggest a compensatory role for endosomal microautophagy when chaperone-mediated autophagy is impaired.

## Abstract

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.

The online version contains supplementary material available at 10.1038/s41598-025-23022-x.