Glycolysis is the central metabolic pathway across all kingdoms of life. Intensive research efforts have been devoted to understanding the tightly orchestrated processes of converting glucose into energy in health and disease. Our review highlights the advances in knowledge of how metabolic and gene networks are integrated through the precise spatiotemporal compartmentalization of rate-limiting enzymes. We provide an overview of technically innovative approaches that have been applied to study phosphofructokinase-1 (PFK1), which represents the fate-determining step of oxidative glucose metabolism. Specifically, we discuss fast-acting chemical biology and optogenetic tools that have delineated new links between metabolite fluxes and transcriptional reprogramming, which operate together to enact tissue-specific processes. Finally, we discuss how recent paradigm-shifting insights into the fundamental basis of glycolytic regulatory control have shed light on the mechanisms of tumorigenesis and could provide insight into new therapeutic vulnerabilities in cancer.
糖酵解是贯穿所有生命界的核心代谢途径。大量研究致力于阐明在生理与病理状态下葡萄糖转化为能量的精密调控过程。本综述重点阐述了通过限速酶的精确时空区室化实现代谢网络与基因网络整合机制的研究进展。我们系统综述了应用于磷酸果糖激酶-1（PFK1）研究的技术创新方法，该酶代表氧化葡萄糖代谢的关键决定步骤。特别探讨了快速作用的化学生物学与光遗传学工具，这些工具揭示了代谢通量与转录重编程之间的新联系，二者协同驱动组织特异性进程。最后，我们讨论了近期关于糖酵解调控基础机制的范式转变认知如何揭示肿瘤发生机制，并为癌症治疗新靶点的发现提供洞见。
肿瘤(癌症)患者之家