The acetylation/acylation (ac(et)ylation) of lysine side chains is a dynamic post-translational modification (PTM) regulating fundamental cellular processes with implications on the organisms’ ageing process: metabolism, transcription, translation, cell proliferation, regulation of the cytoskeleton and DNA damage repair. First identified to occur on histones, later studies revealed the presence of lysine ac(et)ylation in organisms of all kingdoms of life, in proteins covering all essential cellular processes. A remarkable finding showed that the NAD+-dependent sirtuin deacetylase Sir2 has an impact on replicative lifespan in Saccharomyces cerevisiae suggesting that lysine acetylation has a direct role in the ageing process. Later studies identified sirtuins as mediators for beneficial effects of caloric/dietary restriction on the organisms’ health- or lifespan. However, the molecular mechanisms underlying these effects are only incompletely understood. Progress in mass-spectrometry, structural biology, synthetic and semi-synthetic biology deepened our understanding of this PTM. This review summarizes recent developments in the research field. It shows how lysine ac(et)ylation regulates protein function, how it is regulated enzymatically and non-enzymatically, how a dysfunction in this post-translational machinery contributes to disease development. A focus is set on sirtuins and lysine acyltransferases as these are direct sensors and mediators of the cellular metabolic state. Finally, this review highlights technological advances to study lysine ac(et)ylation.

中文翻译：

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翻译后赖氨酸乙酰化在健康、衰老和疾病中的作用

赖氨酸侧链的乙酰化/酰化 (ac(et)ylation) 是一种动态的翻译后修饰 (PTM)，它调节基本的细胞过程，对生物体的衰老过程有影响：代谢、转录、翻译、细胞增殖、调节细胞骨架和 DNA 损伤修复。最初发现发生在组蛋白上，后来的研究揭示了赖氨酸乙酰化在所有生命王国的生物体中的存在，在涵盖所有基本细胞过程的蛋白质中。一项显着的发现表明，NAD+依赖的sirtuin脱乙酰酶Sir2对复制寿命有影响酿酒酵母表明赖氨酸乙酰化在衰老过程中具有直接作用。后来的研究将sirtuins确定为热量/饮食限制对生物体健康或寿命的有益影响的介质。然而，这些影响背后的分子机制尚不完全清楚。质谱、结构生物学、合成和半合成生物学的进展加深了我们对这一 PTM 的理解。本综述总结了该研究领域的最新进展。它显示了赖氨酸乙酰化如何调节蛋白质功能，它如何通过酶促和非酶促调节，这种翻译后机制中的功能障碍如何促进疾病发展。重点关注去乙酰化酶和赖氨酸酰基转移酶，因为它们是细胞代谢状态的直接传感器和介质。最后，