线粒体作为信号细胞器控制哺乳动物干细胞命运。
Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate.
机构信息
Department of Medicine, Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Department of Medicine, Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
出版信息
Cell Stem Cell. 2021 Mar 4;28(3):394-408. doi: 10.1016/j.stem.2021.02.011.
Abstract
Recent evidence supports the notion that mitochondrial metabolism is necessary for the determination of stem cell fate. Historically, mitochondrial metabolism is linked to the production of ATP and tricarboxylic acid (TCA) cycle metabolites to support stem cell survival and growth, respectively. However, it is now clear that beyond these canonical roles, mitochondria as signaling organelles dictate stem cell fate and function. In this review, we focus on key conceptual ideas on how mitochondria control mammalian stem cell fate and function through reactive oxygen species (ROS) generation, TCA cycle metabolite production, NAD/NADH ratio regulation, pyruvate metabolism, and mitochondrial dynamics.
摘要
最近的证据支持这样一种观点，即线粒体代谢对于干细胞命运的决定是必要的。从历史上看，线粒体代谢与三羧酸 (TCA) 循环代谢物的产生有关，分别支持干细胞的存活和生长。然而，现在很明显，除了这些典型作用之外，线粒体作为信号细胞器决定了干细胞的命运和功能。在这篇综述中，我们重点介绍了关于线粒体如何通过生成活性氧 (ROS)、TCA 循环代谢物产生、NAD/NADH 比调节、丙酮酸代谢和线粒体动力学来控制哺乳动物干细胞命运和功能的关键概念。
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1
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Cell Metab. 2020 Dec 1;32(6):920-937. doi: 10.1016/j.cmet.2020.10.011. Epub 2020 Nov 19.
2
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Cell Metab. 2020 Nov 3;32(5):889-900.e7. doi: 10.1016/j.cmet.2020.10.005.
3
Metabolic Coordination of Cell Fate by α-Ketoglutarate-Dependent Dioxygenases.α-酮戊二酸依赖性双加氧酶对细胞命运的代谢调控。
Trends Cell Biol. 2021 Jan;31(1):24-36. doi: 10.1016/j.tcb.2020.09.010. Epub 2020 Oct 19.
4
The evolving metabolic landscape of chromatin biology and epigenetics.染色质生物学和表观遗传学的不断变化的代谢景观。
Nat Rev Genet. 2020 Dec;21(12):737-753. doi: 10.1038/s41576-020-0270-8. Epub 2020 Sep 9.
5
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6
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Nat Metab. 2020 Feb;2(2):127-129. doi: 10.1038/s42255-020-0172-2.
7
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Nature. 2020 Sep;585(7824):288-292. doi: 10.1038/s41586-020-2475-6. Epub 2020 Jul 8.
8
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9
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10
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Cell Metab. 2020 Jun 2;31(6):1052-1067. doi: 10.1016/j.cmet.2020.04.022. Epub 2020 May 19.
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