Caligaris Marco, Sampaio-Marques Belém, Hatakeyama Riko, Pillet Benjamin, Ludovico Paula, De Virgilio Claudio, Winderickx Joris, Nicastro Raffaele
Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal.
J Fungi (Basel). 2023 Jul 26;9(8):787. doi: 10.3390/jof9080787.
Yeast cells are equipped with different nutrient signaling pathways that enable them to sense the availability of various nutrients and adjust metabolism and growth accordingly. These pathways are part of an intricate network since most of them are cross-regulated and subject to feedback regulation at different levels. In yeast, a central role is played by Sch9, a protein kinase that functions as a proximal effector of the conserved growth-regulatory TORC1 complex to mediate information on the availability of free amino acids. However, recent studies established that Sch9 is more than a TORC1-effector as its activity is tuned by several other kinases. This allows Sch9 to function as an integrator that aligns different input signals to achieve accuracy in metabolic responses and stress-related molecular adaptations. In this review, we highlight the latest findings on the structure and regulation of Sch9, as well as its role as a nutrient-responsive hub that impacts on growth and longevity of yeast cells. Given that most key players impinging on Sch9 are well-conserved, we also discuss how studies on Sch9 can be instrumental to further elucidate mechanisms underpinning healthy aging in mammalians.
酵母细胞配备了不同的营养信号通路，使它们能够感知各种营养物质的可用性，并相应地调整新陈代谢和生长。这些通路是一个复杂网络的一部分，因为它们中的大多数都是交叉调节的，并在不同水平上受到反馈调节。在酵母中，Sch9起着核心作用，它是一种蛋白激酶，作为保守的生长调节TORC1复合体的近端效应器，介导关于游离氨基酸可用性的信息。然而，最近的研究表明，Sch9不仅仅是一种TORC1效应器，因为它的活性受到其他几种激酶的调节。这使得Sch9能够作为一个整合器，整合不同的输入信号，以实现代谢反应和应激相关分子适应的准确性。在这篇综述中，我们重点介绍了关于Sch9的结构和调节的最新发现，以及它作为一个营养反应枢纽对酵母细胞生长和寿命的影响。鉴于影响Sch9的大多数关键因子都高度保守，我们还讨论了对Sch9的研究如何有助于进一步阐明哺乳动物健康衰老的机制。
