Size-Specific Modulation of a Multienzyme Glucosome Assembly during the Cell Cycle.
Size-Specific Modulation of a Multienzyme Glucosome Assembly during the Cell Cycle.
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DOI：
10.1021/acsbiomedchemau.3c00037
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发表时间：
2023-10-18
期刊：
影响因子：
--
通讯作者：
An, Songon
中科院分区：
文献类型：
--
作者：
Jeon, Miji;Schmitt, Danielle L;Kyoung, Minjoung;An, Songon
葡萄糖代谢中的酶已经进行了大量的研究，揭示了它们在细胞周期中的生物学作用的重要性。然而，由于缺乏可行的实验策略来测量酶的活性，特别是在活的人类细胞中，它一直具有挑战性，以解决他们的酶活性，从而预期的葡萄糖流量是否与细胞周期进程直接相关。人类细胞如何在亚细胞水平上调节葡萄糖代谢以满足细胞周期中的代谢需求，这在很大程度上仍然是难以捉摸的。同时，我们的特点是，在葡萄糖代谢的速率决定酶在空间上组织成三个不同大小的多酶代谢组件，称为glucosomes，调节能量代谢和积木生物合成之间的葡萄糖流量。在这项工作中，我们首先确定使用细胞同步化和流式细胞术技术，增强的绿色荧光蛋白标记的磷酸果糖激酶是足够的细胞内生物标志物，以评估在细胞周期中的葡萄糖代谢的状态。然后，我们应用荧光单细胞成像策略，发现显示小尺寸的糖体的Hs578 T细胞的百分比在细胞周期期间急剧变化，而具有中等尺寸的糖体的细胞的百分比仅在G1期显著升高，但显示大尺寸的糖体的细胞的百分比几乎没有或最小限度地改变沿着细胞周期。如果我们考虑我们以前的定位功能的研究，显示组装大小依赖的代谢作用的葡萄糖体，这项工作强烈表明，葡萄糖体的大小在细胞周期中调节糖酵解和积木生物合成之间的葡萄糖流量。因此，我们提出了葡萄糖体的大小特异性调制作为一种幕后机制，可以解释葡萄糖代谢与细胞周期的功能关联，从而解释它们在人类细胞生物学中的代谢意义。
Enzymes in glucose metabolism have been subjected to numerous studies, revealing the importance of their biological roles during the cell cycle. However, due to the lack of viable experimental strategies for measuring enzymatic activities particularly in living human cells, it has been challenging to address whether their enzymatic activities and thus anticipated glucose flux are directly associated with cell cycle progression. It has remained largely elusive how human cells regulate glucose metabolism at a subcellular level to meet the metabolic demands during the cell cycle. Meanwhile, we have characterized that rate-determining enzymes in glucose metabolism are spatially organized into three different sizes of multienzyme metabolic assemblies, termed glucosomes, to regulate the glucose flux between energy metabolism and building block biosynthesis. In this work, we first determined using cell synchronization and flow cytometric techniques that enhanced green fluorescent protein-tagged phosphofructokinase is adequate as an intracellular biomarker to evaluate the state of glucose metabolism during the cell cycle. We then applied fluorescence single-cell imaging strategies and discovered that the percentage of Hs578T cells showing small-sized glucosomes is drastically changed during the cell cycle, whereas the percentage of cells with medium-sized glucosomes is significantly elevated only in the G1 phase, but the percentage of cells showing large-sized glucosomes is barely or minimally altered along the cell cycle. Should we consider our previous localization–function studies that showed assembly size-dependent metabolic roles of glucosomes, this work strongly suggests that glucosome sizes are modulated during the cell cycle to regulate glucose flux between glycolysis and building block biosynthesis. Therefore, we propose the size-specific modulation of glucosomes as a behind-the-scenes mechanism that may explain functional association of glucose metabolism with the cell cycle and, thereby, their metabolic significance in human cell biology.
小是美丽的-A糖酵解代谢物信号MTORC1在癌细胞代谢中的激活。
影响因子：
39.3
作者：
Otto AM
通讯作者：
Otto AM