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 (Δopi3) 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.

内质网（ER）作为最大的细胞器，是蛋白质初步加工和磷脂合成的主要场所。磷脂双层是内质网的主要成分，因此它在内质网中蛋白质合成的稳态中起着直观的重要作用。尽管它们的重要性，但黑曲霉中磷脂稳态与蛋白质加工之间的关系仍然知之甚少。在这项研究中，通过敲除磷脂合成或UPR效应子hacA中的关键基因，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。。通过整体转录组和脂质组分析，揭示了磷脂失衡与ER蛋白分泌失衡之间的关系：细胞通过增强蛋白加工和磷脂合成来补偿由ER蛋白分泌不足或磷脂缺乏引起的损害。转录水平，因此磷脂缺乏症（Δopi3）和UPR的持续激活（hacAi）在促进蛋白质分泌和磷脂生物合成方面具有协同作用。同时，磷脂稳态的代谢缺陷和ER蛋白的加工缺陷也将导致细胞对氧化应激，细胞壁抑制和DNA损伤敏感。