Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA.
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA.
Immunol Rev. 2023 Aug;317(1):71-94. doi: 10.1111/imr.13200. Epub 2023 Mar 31.
The mevalonate pathway is an essential metabolic pathway in T cells regulating development, proliferation, survival, differentiation, and effector functions. The mevalonate pathway is a complex, branched pathway composed of many enzymes that ultimately generate cholesterol and nonsterol isoprenoids. T cells must tightly control metabolic flux through the branches of the mevalonate pathway to ensure sufficient isoprenoids and cholesterol are available to meet cellular demands. Unbalanced metabolite flux through the sterol or the nonsterol isoprenoid branch is metabolically inefficient and can have deleterious consequences for T cell fate and function. Accordingly, there is tight regulatory control over metabolic flux through the branches of this essential lipid synthetic pathway. In this review we provide an overview of how the branches of the mevalonate pathway are regulated in T cells and discuss our current understanding of the relationship between mevalonate metabolism, cholesterol homeostasis and T cell function.
甲羟戊酸途径是调节 T 细胞发育、增殖、存活、分化和效应功能的必需代谢途径。甲羟戊酸途径是一个复杂的分支途径，由许多最终产生胆固醇和非甾体异戊二烯的酶组成。T 细胞必须严格控制甲羟戊酸途径分支的代谢通量，以确保有足够的异戊二烯和胆固醇来满足细胞的需求。通过固醇或非甾体异戊二烯分支的不平衡代谢物通量是代谢效率低下的，并且会对 T 细胞命运和功能产生有害影响。因此，对这条必需脂质合成途径分支的代谢通量有严格的调控。在这篇综述中，我们概述了甲羟戊酸途径的分支在 T 细胞中是如何被调控的，并讨论了我们目前对甲羟戊酸代谢、胆固醇稳态和 T 细胞功能之间关系的理解。
