Nucleic Acid Chemistry and Engineering Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa, Japan.
J Cell Biochem. 2024 Nov;125(11):e30377. doi: 10.1002/jcb.30377. Epub 2023 Feb 6.
Sirtuins and autophagy are well-characterized agents that can promote longevity and protect individual organisms from age-associated diseases like neurodegenerative disorders. In recent years, more and more data has been obtained that discerned potential overlaps and crosstalk between Sirtuin proteins and autophagic activity. This review aims to summarize the advances within the field for each individual Sirtuin in mammalian systems. In brief, most Sirtuins have been implicated in promoting autophagy, with Sirtuin 1 and Sirtuin 6 showing the highest immediate involvement, while Sirtuin 4 and Sirtuin 5 only demonstrate occasional influence. The way Sirtuins regulate autophagy, however, is very diverse, as they have been shown to regulate gene expression of autophagy-associated genes and posttranslational modifications of proteins, with consequences for the activity and cellular localization of these proteins. They have also been shown to determine specific proteins for autophagic degradation. Overall, much data has been accumulated over recent years, yet many open questions remain. Especially although the dynamic between Sirtuin proteins and the immediate regulation of autophagic players like Light Chain 3B has been confirmed, many of these proteins have various orthologues in mammalian systems, and research so far has not exceeded the bona fide components of autophagy.
沉默调节蛋白和自噬是经过充分研究的物质,它们可以促进长寿并保护个体生物免受与年龄相关的疾病的影响,如神经退行性疾病。近年来,越来越多的数据表明沉默调节蛋白和自噬活性之间存在潜在的重叠和相互作用。这篇综述旨在总结哺乳动物系统中每种沉默调节蛋白在该领域的进展。简而言之,大多数沉默调节蛋白都被认为可以促进自噬,其中沉默调节蛋白 1 和沉默调节蛋白 6 显示出最高的直接参与度,而沉默调节蛋白 4 和沉默调节蛋白 5 仅偶尔表现出影响。然而,沉默调节蛋白调节自噬的方式非常多样化,因为它们已被证明可以调节自噬相关基因的基因表达和蛋白质的翻译后修饰,从而影响这些蛋白质的活性和细胞定位。它们还被证明可以决定自噬降解的特定蛋白质。总的来说,近年来积累了大量数据,但仍有许多悬而未决的问题。特别是,虽然已经证实了沉默调节蛋白和自噬相关蛋白(如 LC3B)的直接调节之间的动态关系,但哺乳动物系统中有许多这些蛋白的同源物,到目前为止,研究还没有超出自噬的真正成分。