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过氧化物酶体与细胞氧化还原/抗氧化平衡:蛋白质氧化还原修饰及其对细胞器间通讯的影响

Peroxisomes and Cellular Oxidant/Antioxidant Balance: Protein Redox Modifications and Impact on Inter-organelle Communication.

作者信息

Fransen Marc, Lismont Celien

机构信息

Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, Box 601, 3000, Louvain, Belgium.

出版信息

Subcell Biochem. 2018;89:435-461. doi: 10.1007/978-981-13-2233-4_19.

Abstract

Disturbances in cellular redox balance have been associated with pro-aging mechanisms and increased risk for various chronic disease states. Multiple lines of evidence indicate that peroxisomes are central players in cellular redox metabolism. Nevertheless, the potential role of this organelle as intracellular redox signaling platform has been largely overlooked for a long time. Fortunately, this situation is now changing. This review provides a snapshot of the current progress in the field, with an emphasis on the situation in mammals. We first briefly introduce the basics of redox biology and how reactive oxygen and nitrogen species can drive cellular signaling events. Next, we discuss current evidence linking peroxisome (dys)function to redox signaling, both in health and disease. We also highlight what is currently known about the downstream targets of peroxisome-derived oxidants. In addition, we present an extensive list of proteins that are involved in peroxisome functioning and have been identified as being responsive to oxidative stress in large scale redox proteomics studies. Finally, we address how changes in peroxisomal redox state may impact on functional mechanisms underlying inter-organelle communication. Gaining more insight into these mechanisms is key to our understanding of how peroxisomes are embedded in cellular signaling networks implicated in aging and diseases such as cancer, diabetes, and neurodegenerative disorders.

摘要

细胞氧化还原平衡的紊乱与衰老机制以及各种慢性疾病状态风险增加有关。多条证据表明,过氧化物酶体是细胞氧化还原代谢的核心参与者。然而,长期以来,这种细胞器作为细胞内氧化还原信号平台的潜在作用在很大程度上被忽视了。幸运的是,这种情况现在正在改变。本综述概述了该领域的当前进展,重点是哺乳动物的情况。我们首先简要介绍氧化还原生物学的基础知识,以及活性氧和氮物种如何驱动细胞信号事件。接下来,我们讨论目前将过氧化物酶体(功能异常)与健康和疾病中的氧化还原信号联系起来的证据。我们还强调了目前对过氧化物酶体衍生氧化剂的下游靶点的了解。此外,我们列出了一份参与过氧化物酶体功能且在大规模氧化还原蛋白质组学研究中被确定对氧化应激有反应的蛋白质清单。最后,我们探讨过氧化物酶体氧化还原状态的变化如何影响细胞器间通讯的功能机制。更深入地了解这些机制是我们理解过氧化物酶体如何嵌入与衰老以及癌症、糖尿病和神经退行性疾病等疾病相关的细胞信号网络的关键。

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