Homeostatic control of stearoyl desaturase expression via patched-like receptor PTR-23 ensures the survival of C. elegans during heat stress.
Homeostatic control of stearoyl desaturase expression via patched-like receptor PTR-23 ensures the survival of C. elegans during heat stress.
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DOI：
10.1371/journal.pgen.1011067
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发表时间：
2023-12
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
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生物体对温度波动的反应包括进化上保守的胞质分子伴侣机制以及细胞膜脂质成分的适应性改变。利用C.作为一个模型系统，我们问是否适应性脂质稳态所需的生理相关的热应激期间的生存。通过对热应激前后蠕虫体内脂质组成的系统分析，我们发现热应激动物体内不饱和脂肪酸减少。这伴随着由fat-1、fat-3、fat-4、fat-5、fat-6和fat-7基因编码的脂肪酸去饱和酶的转录下调。相反，负责PUFA前体油酸合成的Δ9去饱和酶FAT-7的过表达和油酸的补充导致蠕虫在热应激期间加速死亡。有趣的是，热应激导致蠕虫表皮的渗透性缺陷。我们发现，脂肪-7的表达减少的渗透性缺陷的胶原蛋白（PDC）突变体，dpy-10，已知具有增强的热应激抗性（HSR）。此外，我们发现，dpy-10动物的HSR依赖于PTR-23的上调，PTR-23是表皮中的一种补丁样受体，并且PTR-23下调fat-7的表达。因此，ptr-23在野生型动物中的废除影响其在热应激期间的存活。本研究为脂肪酸去饱和酶在梭菌索马胞体表达的负调控提供了证据。elegans通过补丁受体信号传导组件的非规范作用。总之，这构成了一个皮肤-肠道轴的调节脂质去饱和，以促进蠕虫在热应激期间的生存。温度波动是所有生物体的主要环境应激源。在这里，我们描述了一种机制，允许多细胞生物协调不同组织之间的热应激反应，以确保更好的生存。我们发现，蠕虫皮肤上的受体控制着成年人的应激反应。该受体调节脂质代谢，以增强慢性热应激期间的细胞健康和生物体存活。
Organismal responses to temperature fluctuations include an evolutionarily conserved cytosolic chaperone machinery as well as adaptive alterations in lipid constituents of cellular membranes. Using C. elegans as a model system, we asked whether adaptable lipid homeostasis is required for survival during physiologically relevant heat stress. By systematic analyses of lipid composition in worms during and before heat stress, we found that unsaturated fatty acids are reduced in heat-stressed animals. This is accompanied by the transcriptional downregulation of fatty acid desaturase enzymes encoded by fat-1, fat-3, fat-4, fat-5, fat-6, and fat-7 genes. Conversely, overexpression of the Δ9 desaturase FAT-7, responsible for the synthesis of PUFA precursor oleic acid, and supplementation of oleic acid causes accelerated death of worms during heat stress. Interestingly, heat stress causes permeability defects in the worm’s cuticle. We show that fat-7 expression is reduced in the permeability defective collagen (PDC) mutant, dpy-10, known to have enhanced heat stress resistance (HSR). Further, we show that the HSR of dpy-10 animals is dependent on the upregulation of PTR-23, a patched-like receptor in the epidermis, and that PTR-23 downregulates the expression of fat-7. Consequently, abrogation of ptr-23 in wild type animals affects its survival during heat stress. This study provides evidence for the negative regulation of fatty acid desaturase expression in the soma of C. elegans via the non-canonical role of a patched receptor signaling component. Taken together, this constitutes a skin-gut axis for the regulation of lipid desaturation to promote the survival of worms during heat stress. Temperature fluctuation is a major environmental stressor for all living organisms. Here, we describe a mechanism that allows multicellular organisms to coordinate heat stress response between different tissues to ensure better survival. We find that a receptor in the skin of the worm controls stress response in adults. The receptor regulates lipid metabolism to enhance cellular health and organismal survival during chronic heat stress.
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