DeMichele Emily, Buret Andre G, Taylor Cormac T
School of Medicine and Systems Biology Ireland, The Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Department of Biological Sciences, University of Calgary, Calgary, AB, Canada.
Pflugers Arch. 2024 Sep;476(9):1353-1368. doi: 10.1007/s00424-024-02953-w. Epub 2024 Apr 4.
Mammalian cells utilize glucose as a primary carbon source to produce energy for most cellular functions. However, the bioenergetic homeostasis of cells can be perturbed by environmental alterations, such as changes in oxygen levels which can be associated with bacterial infection. Reduction in oxygen availability leads to a state of hypoxia, inducing numerous cellular responses that aim to combat this stress. Importantly, hypoxia strongly augments cellular glycolysis in most cell types to compensate for the loss of aerobic respiration. Understanding how this host cell metabolic adaptation to hypoxia impacts the course of bacterial infection will identify new anti-microbial targets. This review will highlight developments in our understanding of glycolytic substrate channeling and spatiotemporal enzymatic organization in response to hypoxia, shedding light on the integral role of the hypoxia-inducible factor (HIF) during host-pathogen interactions. Furthermore, the ability of intracellular and extracellular bacteria (pathogens and commensals alike) to modulate host cellular glucose metabolism will be discussed.
哺乳动物细胞利用葡萄糖作为主要碳源，为大多数细胞功能产生能量。然而，细胞的生物能量稳态可能会受到环境变化的干扰，例如与细菌感染相关的氧气水平变化。氧气供应减少会导致缺氧状态，引发许多旨在对抗这种应激的细胞反应。重要的是，缺氧在大多数细胞类型中会强烈增强细胞糖酵解，以补偿有氧呼吸的损失。了解宿主细胞对缺氧的代谢适应如何影响细菌感染的进程将有助于确定新的抗菌靶点。本综述将重点介绍我们对缺氧反应中糖酵解底物通道化和时空酶组织的理解进展，揭示缺氧诱导因子（HIF）在宿主-病原体相互作用中的重要作用。此外，还将讨论细胞内和细胞外细菌（病原体和共生菌）调节宿主细胞葡萄糖代谢的能力。
