小柯机器人

美国哈佛医学院David M. Sabatini等研究人员合作发现，Sestrin介导果蝇对低亮氨酸饮食的检测和适应。相关论文于2022年7月20日在线发表在《自然》杂志上。

研究人员发现Sestrin缺失的果蝇（Sesn^-/-）在急性亮氨酸饥饿后不能抑制mTORC1或激活自噬，在低亮氨酸饮食中发育受损，寿命缩短。表达白氨酸结合缺陷的Sestrin突变体（Sesn^L431E）的基因敲入果蝇具有减少的、对亮氨酸不敏感的mTORC1活性。值得注意的是，研究人员发现国蝇可以区分含或不含亮氨酸的食物，并优先在含亮氨酸的食物上进食和产下后代。这种偏好取决于Sestrin及其与亮氨酸结合的能力。亮氨酸调节胶质细胞中的mTORC1活性，敲除这些细胞中的Sesn会降低果蝇检测无亮氨酸食物的能力。因此，mTORC1对营养的感知是必要的，这不仅是为了让果蝇适应，也是为了检测缺乏基本营养的食物。

据介绍，mTORC1调节细胞的生长和代谢，从而应对多种营养物质，包括必需氨基酸亮氨酸。最近在培养的哺乳动物细胞中发现，Sestrin是一种与亮氨酸结合的蛋白，在亮氨酸缺失期间抑制mTORC1的信号传导，但它们在生物体对饮食亮氨酸的反应中的作用仍不明确。

附：英文原文

Title: Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila

Author: Gu, Xin, Jouandin, Patrick, Lalgudi, Pranav V., Binari, Rich, Valenstein, Max L., Reid, Michael A., Allen, Annamarie E., Kamitaki, Nolan, Locasale, Jason W., Perrimon, Norbert, Sabatini, David M.

Issue&Volume: 2022-07-20

Abstract: Mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth and metabolism in response to multiple nutrients, including the essential amino acid leucine1. Recent work in cultured mammalian cells established the Sestrins as leucine-binding proteins that inhibit mTORC1 signalling during leucine deprivation2,3, but their role in the organismal response to dietary leucine remains elusive. Here we find that Sestrin-null flies (Sesn/) fail to inhibit mTORC1 or activate autophagy after acute leucine starvation and have impaired development and a shortened lifespan on a low-leucine diet. Knock-in flies expressing a leucine-binding-deficient Sestrin mutant (SesnL431E) have reduced, leucine-insensitive mTORC1 activity. Notably, we find that flies can discriminate between food with or without leucine, and preferentially feed and lay progeny on leucine-containing food. This preference depends on Sestrin and its capacity to bind leucine. Leucine regulates mTORC1 activity in glial cells, and knockdown of Sesn in these cells reduces the ability of flies to detect leucine-free food. Thus, nutrient sensing by mTORC1 is necessary for flies not only to adapt to, but also to detect, a diet deficient in an essential nutrient.

DOI: 10.1038/s41586-022-04960-2

Source: https://www.nature.com/articles/s41586-022-04960-2

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