UFL1 regulates cellular homeostasis by targeting endoplasmic reticulum and mitochondria in NEFA-stimulated bovine mammary epithelial cells via the IRE1α/XBP1 pathway.
Free Radic Biol Med
; 222: 16-26, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38821134
ABSTRACT
Elevated levels of NEFA caused by negative energy balance in transition cows induce cellular dyshomeostasis. Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) can maintain cellular homeostasis and act as a critical regulator of stress responses besides functioning in the ubiquitin-like system. The objective of this study was to elucidate the UFL1 working mechanism on promoting cellular adaptations in bovine mammary epithelial cells (BMECs) in response to NEFA challenge, with an emphasis on the ER and mitochondrial function. The results showed that exogenous NEFA and UFL1 depletion resulted in the disorder of ER and mitochondrial homeostasis and the damage of BMEC integrity, overexpression of UFL1 effectively alleviated the NEFA-induced cellular dyshomeostasis. Mechanistically, our study found that UFL1 had a strong interaction with IRE1α and could modulate the IRE1α/XBP1 pathway of unfolded protein response in NEFA-stimulated BMECs, thereby contributing to the modulation of cellular homeostasis. These findings imply that targeting UFL1 may be a therapeutic alternative to relieve NEB-induced metabolic changes in perinatal dairy cows.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Protein Serine-Threonine Kinases
/
Endoplasmic Reticulum
/
Endoribonucleases
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Epithelial Cells
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X-Box Binding Protein 1
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Homeostasis
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Mammary Glands, Animal
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Mitochondria
Limits:
Animals
Language:
En
Journal:
Free Radic Biol Med
Journal subject:
BIOQUIMICA
/
MEDICINA
Year:
2024
Document type:
Article
Country of publication:
United States