Campos Melissa, Albrecht Lauren V
Department of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, CA 92697, USA.
Department of Pharmaceutical Sciences, School of Pharmacy & Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA.
Cancers (Basel). 2023 Dec 19;16(1):16. doi: 10.3390/cancers16010016.
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.
糖酵解是所有生命王国中的核心代谢途径。人们投入了大量的研究精力来理解在健康和疾病状态下将葡萄糖转化为能量的紧密协调过程。我们的综述强调了关于代谢和基因网络如何通过限速酶的精确时空分隔进行整合的知识进展。我们概述了已应用于研究磷酸果糖激酶-1（PFK1）的技术创新方法，PFK1代表氧化葡萄糖代谢的命运决定步骤。具体而言，我们讨论了快速作用的化学生物学和光遗传学工具，这些工具描绘了代谢物通量与转录重编程之间的新联系，它们共同作用以实现组织特异性过程。最后，我们讨论了最近对糖酵解调节控制基本基础的范式转变见解如何揭示肿瘤发生机制，并可能为癌症新的治疗弱点提供见解。
