Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Res Microbiol. 2023 Mar-Apr;174(3):103996. doi: 10.1016/j.resmic.2022.103996. Epub 2022 Oct 31.
The unfolded protein response (UPR) is an important pathway to prevent endoplasmic reticulum (ER) stress in eukaryotic cells. In Saccharomyces cerevisiae, Ire1 is a key regulatory factor required for HAC1 gene splicing for further production of functional Hac1 and activation of UPR gene expression. Autophagy is another mechanism involved in the attenuation of ER stress by ER-phagy, and Atg8 is a core protein in autophagy. Both autophagy and UPR are critical for ER stress response, but whether they act individually or in combination in Candida albicans is unknown. In this study, we explored the interaction between Ire1 and the autophagy protein Atg8 for the ER stress response by constructing the atg8Δ/Δire1Δ/Δ double mutant in the pathogenic fungus C. albicans. Compared to the single mutants atg8Δ/Δ or ire1Δ/Δ, atg8Δ/Δire1Δ/Δ exhibited much higher sensitivity to various ER stress-inducing agents and more severe attenuation of UPR gene expression under ER stress. Further investigations showed that the double mutant had a defect in ER-phagy, which was associated with attenuated vacuolar fusion under ER stress. This study revealed that Ire1 and Atg8 in combination function in the activation of the UPR and ER-phagy to maintain ER homeostasis under ER stress in C. albicans.
未折叠蛋白反应 (UPR) 是防止真核细胞内质网 (ER) 应激的重要途径。在酿酒酵母中，IRE1 是 HAC1 基因剪接所必需的关键调节因子，以进一步产生功能性 Hac1 并激活 UPR 基因表达。自噬是通过 ER 噬作用减轻 ER 应激的另一种机制，而 Atg8 是自噬中的核心蛋白。自噬和 UPR 对于 ER 应激反应都很重要，但在白色念珠菌中它们是单独作用还是联合作用尚不清楚。在这项研究中，我们通过构建致病性真菌白色念珠菌中的 atg8Δ/Δire1Δ/Δ 双突变体，探索了 Ire1 和自噬蛋白 Atg8 之间在 ER 应激反应中的相互作用。与单突变体 atg8Δ/Δ 或 ire1Δ/Δ 相比，atg8Δ/Δire1Δ/Δ 对各种 ER 应激诱导剂更敏感，并且在 ER 应激下 UPR 基因表达的衰减更为严重。进一步的研究表明，该双突变体在 ER 噬作用中存在缺陷，这与 ER 应激下液泡融合减弱有关。这项研究揭示了 Ire1 和 Atg8 在激活 UPR 和 ER 噬作用以维持 ER 平衡方面的组合功能在白色念珠菌的 ER 应激下。
