Loss of heat shock factor initiates intracellular lipid surveillance by actin destabilization.
Loss of heat shock factor initiates intracellular lipid surveillance by actin destabilization.
复制标题
DOI：
10.1016/j.celrep.2022.111493
复制
发表时间：
2022-10-18
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞感知压力并启动反应途径以维持脂质和蛋白质稳态。然而，这些适应机制之间的相互作用尚不清楚。在此，我们展示了细胞溶质蛋白质稳态的不平衡如何影响细胞内脂质的监测。独立于其古老的热保护特性，热休克因子HSF-1通过后生动物特异性核激素受体NHR-49调节脂质代谢和年龄调节。降低hsf-1表达使秀丽隐杆线虫肠肌动蛋白网络不稳定，随后破坏Rab GTP酶介导的运输和营养转运蛋白的细胞表面驻留。随后的吸收不良限制了脂质的可用性，从而通过NHR-49的囊泡释放和核转位激活细胞内脂质监视反应，以增加营养吸收并恢复脂质稳态。总体而言，这些调节细胞溶质蛋白质稳态和脂质监测之间的合作，确保代谢健康和年龄的进展，通过肌动蛋白的完整性，内吞再循环，和脂质传感。Watterson等人描述了HSF-1影响脂质体内平衡的机制。通过其稳定肠肌动蛋白网络的能力，HSF-1促进膜运输，细胞吸收和脂质积累。hsf-1的缺失通过NHR-49激活细胞内脂质监视途径，从而将细胞溶质蛋白质稳态与脂质代谢联系起来。
Cells sense stress and initiate response pathways to maintain lipid and protein homeostasis. However, the interplay between these adaptive mechanisms is unclear. Herein, we demonstrate how imbalances in cytosolic protein homeostasis affect intracellular lipid surveillance. Independent of its ancient thermo-protective properties, the heat shock factor, HSF-1, modulates lipid metabolism and age regulation through the metazoan-specific nuclear hormone receptor, NHR-49. Reduced hsf-1 expression destabilizes the Caenorhabditis elegans enteric actin network, subsequently disrupting Rab GTPase-mediated trafficking and cell-surface residency of nutrient transporters. The ensuing malabsorption limits lipid availability, thereby activating the intracellular lipid surveillance response through vesicular release and nuclear translocation of NHR-49 to both increase nutrient absorption and restore lipid homeostasis. Overall, cooperation between these regulators of cytosolic protein homeostasis and lipid surveillance ensures metabolic health and age progression through actin integrity, endocytic recycling, and lipid sensing. Watterson et al. describe a mechanism through which HSF-1 affects lipid homeostasis. Through its ability to stabilize the enteric actin network, HSF-1 promotes membrane trafficking, cellular absorption, and lipid accumulation. Loss of hsf-1 activates the intracellular lipid surveillance pathway via NHR-49, thereby linking cytosolic protein homeostasis with lipid metabolism.