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A two-way relationship between histone acetylation and metabolism. 组蛋白乙酰化与新陈代谢之间的双向关系
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-12-01 Epub Date: 2024-11-07 DOI: 10.1016/j.tibs.2024.10.005
Evelina Charidemou, Antonis Kirmizis

A link between epigenetics and metabolism was initially recognized because the cellular metabolic state is communicated to the genome through the concentration of intermediary metabolites that are cofactors of chromatin-modifying enzymes. Recently, an additional interaction was postulated due to the capacity of the epigenome to store substantial amounts of metabolites that could become available again to cellular metabolite pools. Here, we focus on histone acetylation and review recent evidence illustrating this reciprocal relationship: in one direction, signaling-induced acetyl-coenzyme A (acetyl-CoA) changes influence histone acetylation levels to regulate genomic functions, and in the opposite direction histone acetylation acts as an acetate reservoir to directly affect downstream acetyl-CoA-mediated metabolism. This review highlights the current understanding, experimental challenges, and future perspectives of this bidirectional interplay.

人们最初认识到表观遗传学与新陈代谢之间的联系，因为细胞的新陈代谢状态是通过作为染色质修饰酶辅助因子的中间代谢物的浓度传递给基因组的。最近，由于表观基因组能够储存大量代谢物，而这些代谢物又可以重新进入细胞代谢物池，因此又推测出了另一种相互作用。在此，我们将重点关注组蛋白乙酰化，并综述了说明这种相互关系的最新证据：在一个方向上，信号诱导的乙酰辅酶 A（乙酰-CoA）变化会影响组蛋白乙酰化水平，从而调节基因组功能；而在另一个相反的方向上，组蛋白乙酰化则充当乙酸盐库，直接影响下游乙酰-CoA 介导的新陈代谢。这篇综述重点介绍了目前对这种双向相互作用的理解、实验挑战和未来展望。
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引用次数: 0
Clues into Wnt cell surface signalosomes and its biogenesis. Wnt 细胞表面信号体及其生物生成的线索。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-12-01 Epub Date: 2024-10-22 DOI: 10.1016/j.tibs.2024.09.007
Philip Schmiege, Xiaochun Li

Wnt morphogens induce signaling via binding their extracellular receptors. Here, we discuss several recent structural studies showing how Wnts engage their receptors frizzled (FZD) and low-density lipoprotein receptor-related protein 5/6 (LRP5/6), how Cachd1 has been shown as an alternative initiator of Wnt signaling, and how lipidated Wnt may be produced and secreted from the cell.

Wnt 形态诱导因子通过结合细胞外受体诱导信号传导。在此，我们讨论了最近的几项结构研究，这些研究显示了 Wnt 如何与其受体 frizzled (FZD) 和低密度脂蛋白受体相关蛋白 5/6 (LRP5/6)结合，Cachd1 如何被证明是 Wnt 信号传导的另一种启动器，以及脂质化 Wnt 如何产生并从细胞中分泌出来。
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引用次数: 0
The role of hydrolysis in perceiving and degrading the plant hormone strigolactones. 水解作用在感知和降解植物激素绞股蓝内酯中的作用。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-12-01 Epub Date: 2024-10-08 DOI: 10.1016/j.tibs.2024.09.006
Kawthar F Alashoor, Jian You Wang, Salim Al-Babili

Strigolactones (SLs) perform versatile functions in plants. The different members of the α/β-hydrolase superfamily bind and hydrolyze SLs at varying rates to transduce their signal or maintain SL homeostasis. Recent work by Palayam et al. on SL-degrading carboxylesterases (CXEs) uncovers structural elements that determine the mechanism, efficiency of SL hydrolysis, and biological functions.

硬脂内酯（SLs）在植物体内具有多种功能。α/β-水解酶超家族的不同成员以不同的速率结合和水解 SLs，以传递其信号或维持 SL 的平衡。Palayam 等人最近对 SL 降解羧基酯酶（CXEs）的研究揭示了决定 SL 水解机制、效率和生物功能的结构要素。
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引用次数: 0
Textbook oxidative phosphorylation needs to be rewritten. 教科书中的氧化磷酸化需要重写。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-21 DOI: 10.1016/j.tibs.2024.11.002
Alicia J Kowaltowski, Fernando Abdulkader

Oxidative phosphorylation (OxPhos) is the energy-transfer process that generates most of our ATP, fueled by proton and electrical gradients across the inner mitochondrial membrane. A new surprising finding by Hernansanz-Agustín et al. demonstrates that between one-third and half of this gradient is attributable to Na+, transported in exchange for protons within complex I.

氧化磷酸化（OxPhos）是产生大部分 ATP 的能量转移过程，其动力来自线粒体内膜上的质子和电梯度。埃尔南桑斯-阿古斯丁（Hernansanz-Agustín）等人的一项新的惊人发现表明，这种梯度的三分之一到一半可归因于Na+，它在复合体 I 中被输送以交换质子。
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引用次数: 0
Subscription and Copyright Information 订阅和版权信息
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/S0968-0004(24)00241-X
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引用次数: 0
Two hearts beat as one: the debate over RAS dimers continues 两心相印：关于 RAS 二聚体的争论仍在继续。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.09.005
Andrew G. Stephen
A recent report by Yun et al. describes the detection of RAS dimers using intact mass spectrometry and investigates the role that membrane lipids, nucleotide state, and binding partners have in their formation.
Yun 等人最近的一篇报告介绍了利用完整质谱检测 RAS 二聚体的方法，并研究了膜脂质、核苷酸状态和结合伙伴在二聚体形成过程中的作用。
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引用次数: 0
Advancing sustainable biotechnology through protein engineering 通过蛋白质工程推进可持续生物技术。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.07.006
Amelia R. Bergeson , Hal S. Alper
The push for industrial sustainability benefits from the use of enzymes as a replacement for traditional chemistry. Biological catalysts, especially those that have been engineered for increased activity, stability, or novel function, and are often greener than alternative chemical approaches. This Review highlights the role of engineered enzymes (and identifies directions for further engineering efforts) in the application areas of greenhouse gas sequestration, fuel production, bioremediation, and degradation of plastic wastes.
使用酶来替代传统化学，有利于推动工业可持续发展。生物催化剂，特别是那些为提高活性、稳定性或新功能而设计的催化剂，通常比替代化学方法更环保。本综述强调了工程酶在温室气体封存、燃料生产、生物修复和塑料废物降解等应用领域的作用（并确定了进一步工程努力的方向）。
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引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/S0968-0004(24)00238-X
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引用次数: 0
The inositol phosphate signalling network in physiology and disease 生理和疾病中的磷酸肌醇信号网络。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.08.005
Seyun Kim , Rashna Bhandari , Charles A. Brearley , Adolfo Saiardi
Combinatorial substitution of phosphate groups on the inositol ring gives rise to a plethora of inositol phosphates (InsPs) and inositol pyrophosphates (PP-InsPs). These small molecules constitute an elaborate metabolic and signalling network that influences nearly every cellular function. This review delves into the knowledge accumulated over the past decades regarding the biochemical principles and significance of InsP metabolism. We focus on the biological actions of InsPs in mammals, with an emphasis on recent findings regarding specific target proteins. We further discuss the roles of InsP metabolism in contributing to physiological homeostasis and pathological conditions. A deeper understanding of InsPs and their metabolic pathways holds the potential to address unresolved questions and propel advances towards therapeutic applications.
肌醇环上磷酸基团的组合取代产生了大量肌醇磷酸盐（InsPs）和肌醇焦磷酸盐（PP-InsPs）。这些小分子构成了一个复杂的代谢和信号网络，影响着几乎所有的细胞功能。本综述深入探讨了过去几十年中积累的有关 InsP 代谢的生化原理和意义的知识。我们重点探讨了 InsPs 在哺乳动物体内的生物作用，并着重介绍了有关特定靶蛋白的最新发现。我们进一步讨论了 InsP 代谢在生理平衡和病理状态中的作用。加深对 InsPs 及其代谢途径的了解有可能解决悬而未决的问题，并推动治疗应用的进展。
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引用次数: 0
New opportunities to overcome T cell dysfunction: the role of transcription factors and how to target them 克服 T 细胞功能障碍的新机遇：转录因子的作用及其靶向方法。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.08.002
Bocheng Wu , Angela N. Koehler , Peter M.K. Westcott
Immune checkpoint blockade (ICB) therapies, which block inhibitory receptors on T cells, can be efficacious in reinvigorating dysfunctional T cell responses. However, most cancers do not respond to these therapies and even in those that respond, tumors can acquire resistance. New strategies are needed to rescue and recruit T cell responses across patient populations and disease states. In this review, we define mechanisms of T cell dysfunction, focusing on key transcription factor (TF) networks. We discuss the complex and sometimes contradictory roles of core TFs in both T cell function and dysfunction. Finally, we review strategies to target TFs using small molecule modulators, which represent a challenging but highly promising opportunity to tune the T cell response toward sustained immunity.
免疫检查点阻断（ICB）疗法可阻断T细胞上的抑制性受体，从而有效重振功能失调的T细胞反应。然而，大多数癌症对这些疗法没有反应，即使有反应的肿瘤也会产生抗药性。我们需要新的策略来挽救和招募不同患者群体和疾病状态下的 T 细胞应答。在这篇综述中，我们定义了 T 细胞功能障碍的机制，重点关注关键转录因子 (TF) 网络。我们讨论了核心 TF 在 T 细胞功能和功能障碍中复杂且有时相互矛盾的作用。最后，我们回顾了使用小分子调节剂靶向 TFs 的策略，这是调整 T 细胞反应以实现持续免疫的一个极具挑战性但又大有希望的机会。
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引用次数: 0
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