Radzinski Meytal, Oppenheim Tal, Metanis Norman, Reichmann Dana
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Institute of Chemistry, Safra Campus Givat Ram, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Biomolecules. 2021 Mar 22;11(3):469. doi: 10.3390/biom11030469.
Protein homeostasis is an essential component of proper cellular function; however, sustaining protein health is a challenging task, especially during the aerobic lifestyle. Natural cellular oxidants may be involved in cell signaling and antibacterial defense; however, imbalanced levels can lead to protein misfolding, cell damage, and death. This merges together the processes of protein homeostasis and redox regulation. At the heart of this process are redox-regulated proteins or thiol-based switches, which carefully mediate various steps of protein homeostasis across folding, localization, quality control, and degradation pathways. In this review, we discuss the "redox code" of the proteostasis network, which shapes protein health during cell growth and aging. We describe the sources and types of thiol modifications and elaborate on diverse strategies of evolving antioxidant proteins in proteostasis networks during oxidative stress conditions. We also highlight the involvement of cysteines in protein degradation across varying levels, showcasing the importance of cysteine thiols in proteostasis at large. The individual examples and mechanisms raised open the door for extensive future research exploring the interplay between the redox and protein homeostasis systems. Understanding this interplay will enable us to re-write the redox code of cells and use it for biotechnological and therapeutic purposes.
蛋白质稳态是细胞正常功能的重要组成部分；然而，维持蛋白质健康是一项具有挑战性的任务，尤其是在有氧生活方式期间。天然细胞氧化剂可能参与细胞信号传导和抗菌防御；然而，水平失衡会导致蛋白质错误折叠、细胞损伤和死亡。这将蛋白质稳态和氧化还原调节过程结合在一起。这一过程的核心是氧化还原调节蛋白或基于硫醇的开关，它们在折叠、定位、质量控制和降解途径中仔细介导蛋白质稳态的各个步骤。在这篇综述中，我们讨论了蛋白质稳态网络的“氧化还原密码”，它在细胞生长和衰老过程中塑造蛋白质健康。我们描述了硫醇修饰的来源和类型，并阐述了在氧化应激条件下蛋白质稳态网络中进化抗氧化蛋白的多种策略。我们还强调了半胱氨酸在不同水平的蛋白质降解中的作用，展示了半胱氨酸硫醇在整体蛋白质稳态中的重要性。所提出的具体例子和机制为未来广泛研究氧化还原和蛋白质稳态系统之间的相互作用打开了大门。理解这种相互作用将使我们能够重新编写细胞的氧化还原密码，并将其用于生物技术和治疗目的。
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