Excessive ER-phagy mediated by FAM134B contributes to trophoblast cell mitochondrial dysfunction in preeclampsia  

作　　者：Andi Wang Zhuo Li Dan Zhang Chang Chen Hua Zhang 

机构地区：[1]Department of Obstetrics and Gynecology,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [2]The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [3]Institute of Life Sciences,Chongqing Medical University,Chongqing 400016,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第10期1446-1459,共14页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.81971406 and 82271715);the 111 Project[No.Yuwaizhuan(2016)32];the Chongqing Science&Technology Commission(No.cstc2021jcyj-msxmX0213);the Natural Science Foundation of Chongqing,China(No.CSTB2022N SCQ-MSX1679);the Chongqing Municipal Education Commission(No.KJZD-K202100407);the Chongqing Health Commission and Chongqing Science&Technology Commission(No.2021MSX M121).

摘　　要：Autophagy dysregulation and Ca2+-induced mitochondrial dysfunction in trophoblast cells are proposed to contribute to preeclampsia(PE)development.FAM134B is identified as a receptor associated with endoplasmic reticulum autophagy(ER-phagy).In this study,the placentas of normal pregnant women and PE patients are collected and analyzed by immunohistochemistry,quantitative real-time PCR,and western blot analysis.The effects of ERphagy are investigated in HTR8/SVneo cells.Significantly increased levels of FAM134B,inositol-1,4,5-triphosphate receptor type 1(IP3R),calnexin,cleaved caspase 3 and cytochrome C are detected in the PE placenta and sodium nitroprusside(SNP)-treated HTR-8/SVneo cells.Overexpression of FAM134B in HTR-8/SVneo cells results in increased apoptosis,impaired invasion capacity,and diminished mitochondrial function,while an autophagy inhibitor improves mitochondrial performance.Excessive ER-phagy is also associated with an increased concentration of gamma linolenic acid.Our findings suggest that FAM134B contributes to trophoblast apoptosis by mediating ER-mitochondria Ca^(2+)transfer through mitochondria-associated endoplasmic reticulum membranes(MAMs)and subsequent mitochondrial function,further enhancing our understanding of PE etiology.

关 键 词：PREECLAMPSIA endoplasmic reticulum autophagy(ER-phagy) mitochondria-associated endoplasmic reticulum membrane mitochondrial dysfunction lipidomic metabolome 

分 类 号：R714.24[医药卫生—妇产科学]