Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell Rep. 2022 Oct 18;41(3):111493. doi: 10.1016/j.celrep.2022.111493.
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.
细胞感知压力并启动响应途径以维持脂质和蛋白质的稳态。然而，这些适应性机制之间的相互作用尚不清楚。本文展示了细胞质蛋白稳态失衡如何影响细胞内脂质监测。热休克因子 HSF-1 独立于其古老的热保护特性，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。hsf-1 表达的降低会破坏秀丽隐杆线虫肠细胞肌动蛋白网络的稳定性，随后破坏 Rab GTPase 介导的营养转运体的运输和细胞表面驻留。随之而来的吸收不良限制了脂质的可用性，从而通过 NHR-49 的囊泡释放和核易位激活细胞内脂质监测反应，以增加营养吸收并恢复脂质稳态。总的来说，细胞质蛋白稳态和脂质监测的这些调节剂之间的合作通过肌动蛋白完整性、内吞循环和脂质感应确保了代谢健康和年龄进展。
