The Role of Citrate Transporter INDY in Metabolism and Stem Cell Homeostasis.

The Role of Citrate Transporter INDY in Metabolism and Stem Cell Homeostasis.
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DOI:
10.3390/metabo11100705
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发表时间:
2021-10-15
期刊:
影响因子:
4.1
通讯作者:
Rogina B
Rogina B
中科院分区:
生物学3区
文献类型:
--
作者:
Kannan K;Rogina B

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I 'm Not Dead Yet (Indy)是一种编码哺乳动物SLC13A5质膜柠檬酸转运蛋白同源基因的苍蝇基因。在果蝇中减少Indy基因的表达,以及它在蠕虫中的同源物,可以延长寿命。果蝇、蠕虫、小鼠和大鼠体内的柠檬酸盐减少会通过调节细胞质柠檬酸盐的水平来影响新陈代谢,从而引发一种类似于卡路里限制的状态。这些变化包括降低血脂水平、增加胰岛素敏感性、增加线粒体生物生成、防止体重增加等。INDY蛋白主要表达于果蝇代谢组织:中肠、脂肪体和卵泡细胞。与Indy基因活性降低相关的苍蝇中肠代谢变化导致线粒体功能保留和活性氧产生减少。所有这些变化导致肠道干细胞稳态的保持,这在维持肠道上皮功能和延长果蝇的健康寿命中起着关键作用。Indy基因表达水平随饮食热量含量、炎症和衰老而变化,表明Indy通过控制柠檬酸盐水平来调节代谢对营养或能量需求的适应。
I’m Not Dead Yet (Indy) is a fly gene that encodes a homologue of mammalian SLC13A5 plasma membrane citrate transporter. Reducing expression of Indy gene in flies, and its homologues in worms, extends longevity. Indy reduction in flies, worms, mice and rats affects metabolism by regulating the levels of cytoplasmic citrate, inducing a state similar to calorie restriction. Changes include lower lipid levels, increased insulin sensitivity, increased mitochondrial biogenesis, and prevention of weight gain, among others. The INDY protein is predominantly expressed in fly metabolic tissues: the midgut, fat body and oenocytes. Changes in fly midgut metabolism associated with reduced Indy gene activity lead to preserved mitochondrial function and reduced production of reactive oxygen species. All these changes lead to preserved intestinal stem cell homeostasis, which has a key role in maintaining intestinal epithelium function and enhancing fly healthspan and lifespan. Indy gene expression levels change in response to caloric content of the diet, inflammation and aging, suggesting that INDY regulates metabolic adaptation to nutrition or energetic requirements by controlling citrate levels.
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