Regulation and function of the mammalian tricarboxylic acid cycle.

Regulation and function of the mammalian tricarboxylic acid cycle.
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DOI:
10.1016/j.jbc.2022.102838
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发表时间:
2023-02
影响因子:
4.8
通讯作者:
Finley, Lydia W. S.
Finley, Lydia W. S.
中科院分区:
生物学2区
文献类型:
--
作者:
Arnold, Paige K.;Finley, Lydia W. S.

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三羧酸(TCA)循环,也被称为克雷布斯循环,是一个中心代谢途径,执行氧化营养物质的基本功能,以支持细胞生物能量学。最近,TCA循环行为是动态的,TCA循环的产物可以在癌症和其他病理状态中被吸收。在这篇综述中,我们重新审视了三羧酸循环,包括它的潜在起源和它的发现历史。我们提供了持续的TCA循环功能和关键调控节点可以刺激或限制TCA循环活动的需求的详细会计。我们还讨论了最近我们对TCA循环接线灵活性的理解以及哺乳动物细胞中TCA循环活性的异质性日益认识的进展。更深入地了解TCA循环如何被不同地调节,从而在不同的环境中配置,将揭示这一途径是如何满足不同哺乳动物细胞状态的需求的。
The tricarboxylic acid (TCA) cycle, otherwise known as the Krebs cycle, is a central metabolic pathway that performs the essential function of oxidizing nutrients to support cellular bioenergetics. More recently, it has become evident that TCA cycle behavior is dynamic, and products of the TCA cycle can be co-opted in cancer and other pathologic states. In this review, we revisit the TCA cycle, including its potential origins and the history of its discovery. We provide a detailed accounting of the requirements for sustained TCA cycle function and the critical regulatory nodes that can stimulate or constrain TCA cycle activity. We also discuss recent advances in our understanding of the flexibility of TCA cycle wiring and the increasingly appreciated heterogeneity in TCA cycle activity exhibited by mammalian cells. Deeper insight into how the TCA cycle can be differentially regulated and, consequently, configured in different contexts will shed light on how this pathway is primed to meet the requirements of distinct mammalian cell states.
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