Disease tolerance is an essential defense strategy against pathogens, alleviating tissue damage regardless of pathogen multiplication. However, its genetic and molecular basis remains largely unknown. Here, we discovered that protein condensation at the endoplasmic reticulum (ER) regulates disease tolerance in Arabidopsis against Pseudomonas syringae. During infection, Hematopoietic protein-1 (HEM1) and Bax-inhibitor 1 (BI-1) coalesce into ER-associated condensates facilitated by their phase-separation behaviors. While BI-1 aids in clearing these condensates via autophagy, it also sequesters lipid-metabolic enzymes within condensates, likely disturbing lipid homeostasis. Consequently, mutations in hem1, which hinder condensate formation, or in bi-1, which prevent enzyme entrapment, enhance tissue-damage resilience, and preserve overall plant health during infection. These findings suggest that the ER is a crucial hub for maintaining cellular homeostasis and establishing disease tolerance. They also highlight the potential of engineering disease tolerance as a defense strategy to complement established resistance mechanisms in combating plant diseases.

疾病耐受性是针对病原体的重要防御策略，无论病原体如何繁殖，都可以减轻组织损伤。然而，其遗传和分子基础仍然很大程度上未知。在这里，我们发现内质网（ER）处的蛋白质浓缩调节拟南芥对丁香假单胞菌的疾病耐受性。在感染过程中，造血蛋白 1 (HEM1) 和 Bax 抑制剂 1 (BI-1) 在其相分离行为的推动下结合成 ER 相关凝聚物。虽然 BI-1 有助于通过自噬清除这些冷凝物，但它也会隔离冷凝物中的脂质代谢酶，可能会扰乱脂质稳态。因此， hem1的突变会阻碍冷凝物的形成，而bi-1 的突变会阻止酶的截留，增强组织损伤的恢复能力，并在感染期间保持植物的整体健康。这些发现表明内质网是维持细胞稳态和建立疾病耐受性的重要枢纽。他们还强调了工程抗病性作为防御策略的潜力，以补充对抗植物病害的既定抗性机制。