UFL1 regulates cellular homeostasis by targeting endoplasmic reticulum and mitochondria in NEFA-stimulated bovine mammary epithelial cells via the IRE1 α /XBP1 pathway

文献类型： 外文期刊

第一作者： Yan, Yexiao

作者： Yan, Yexiao;Huang, Junpeng;Li, Yuan;Zhao, Weiguo;Li, Chengmin;Yan, Yexiao;Huang, Junpeng;Li, Yuan;Zhao, Weiguo;Li, Chengmin;Chen, Xiangxing

作者机构：

关键词： UFL1; Cellular homeostasis; IRE1 alpha/XBP1 pathway; NEFA; Bovine mammary epithelial cells

期刊名称：FREE RADICAL BIOLOGY AND MEDICINE （ 影响因子：7.1； 五年影响因子：7.9 ）

ISSN： 0891-5849

年卷期： 2024 年 222 卷

页码：

收录情况： SCI

摘要： 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 IRE1 alpha and could modulate the IRE1 alpha/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.

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