Study on the interaction mechanism of phospholipid imbalance and endoplasmic reticulum protein secretion imbalance in Aspergillus niger
Study on the interaction mechanism of phospholipid imbalance and endoplasmic reticulum protein secretion imbalance in Aspergillus niger
复制标题
黑曲霉磷脂失衡与内质网蛋白分泌失衡互作机制研究
DOI：
10.1016/j.bbamem.2020.183530
复制
发表时间：
2021-03-01
影响因子：
3.4
通讯作者：
Pan, Li
中科院分区：
文献类型：
--
作者：
Dong, Hongzhi;Wang, Bin;Pan, Li
内质网（ER）是最大的膜细胞器，是蛋白质初步加工和磷脂合成的主要场所。磷脂双分子层是内质网的主要组成部分，对内质网蛋白质合成的稳态起着直观的重要作用。尽管它们的重要性，磷脂稳态和蛋白质加工在尼日尔之间的关系仍然知之甚少。本研究通过敲除磷脂合成关键基因或UPR效应子hacA，建立了磷脂酰乙醇胺（PE）/磷脂酰胆碱（PC）和磷脂酰酸（PA）代谢突变体和ER蛋白加工突变体。基于全局转录组和脂质组分析，磷脂失衡与ER蛋白分泌失衡之间的关系揭示如下：细胞通过在转录水平上增强蛋白质加工和磷脂的合成来补偿ER蛋白分泌不足或磷脂不足引起的损伤，因此，磷脂缺乏（Δ opi 3）和UPR的持续激活（hacAi）在促进蛋白质分泌和磷脂生物合成中具有协同作用。同时，磷脂稳态的代谢缺陷和ER蛋白的加工缺陷也会引起细胞对氧化应激的敏感性、细胞壁抑制和DNA损伤。
As the largest membrane organelle, the endoplasmic reticulum (ER) is the main location for protein preliminary processing and phospholipid synthesis. Phospholipid bilayer is the main component of the ER, so it plays an intuitively important role in the steady state of protein synthesis in the ER. Despite of their importance, relationship between phospholipid homeostasis and protein processing in Aspergillus niger remains poorly understood. In this study, phosphatidyl ethanolamine (PE)/phosphatidyl choline (PC) and phosphatidyl acid (PA) metabolic mutants and ER protein processing mutants were established by knockout the key genes in phospholipid synthesis or UPR effector hacA. Based on global transcriptome and lipidome analysis, the relationship between the phospholipids imbalance and ER protein secretory imbalance was revealed as followed: The cells compensate for the damage caused by ER protein secretory deficiency or phospholipid deficiency from enhancing the protein processing and the synthesis of phospholipids at the transcription level, therefore phospholipid deficiency (Delta opi3) and continuous activation of UPR (hacAi) have a synergistic effect in promoting protein secretion and phospholipid biosynthesis. At the same time, the metabolic deficiencies of phospholipid homeostasis and the processing deficiencies of ER protein will also cause cells sensitive to oxidative stress, cell wall inhibition and DNA damage.