School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Cell Biochem Funct. 2023 Dec;41(8):1514-1525. doi: 10.1002/cbf.3892. Epub 2023 Nov 28.
Nutrient-sensing plays a crucial role in maintaining cellular energy and metabolic homeostasis. Perturbations in sensing pathways are associated with a wide variety of pathologies, especially metabolic diseases. Very little is understood about sensing fluctuations in nutrients and how this information is integrated into physiological and metabolic adaptation that could further affect cell-fate decisions during differentiation in Dictyostelium discoideum (henceafter, Dictyostelium). Glucose is the primary metabolic fuel among all nutrients. Carbohydrates, lipids and proteins ultimately breakdown into glucose, which is further used for providing energy. The maintenance of optimum glucose levels is important for efficient cell-survival. Glucose is not only a nutrient, but also a signaling molecule influencing cell growth and differentiation in Dictyostelium. Modulation of endogenous glucose levels either by varying exogenous glucose levels or genetic overexpression or deletion of genes involved in glucose signaling lead to changes in endogenous metabolite levels such as ADP/ATP ratio, NAD /NADH ratio, cAMP and ROS levels which further influence cell-fate decisions. Here, we show that AMPKα and Sir2D are components of glucose-signaling pathway in Dictyostelium which adjust cell metabolism interdependently in response to nutrient-status and promote cell-fate decisions.
营养感应在维持细胞能量和代谢稳态方面起着至关重要的作用。感应途径的紊乱与各种病理有关，特别是代谢疾病。人们对感应营养波动以及如何将这些信息整合到生理和代谢适应中的了解甚少，这可能会进一步影响分化过程中的细胞命运决定。在盘基网柄菌（此后称为盘基网柄菌）中。葡萄糖是所有营养物质中的主要代谢燃料。碳水化合物、脂肪和蛋白质最终分解成葡萄糖，葡萄糖进一步用于提供能量。维持最佳葡萄糖水平对于有效细胞存活很重要。葡萄糖不仅是一种营养物质，还是一种信号分子，影响盘基网柄菌中的细胞生长和分化。通过改变外源性葡萄糖水平或遗传过表达或缺失参与葡萄糖信号的基因来调节内源性葡萄糖水平，导致内源性代谢物水平（如 ADP/ATP 比、NAD/NADH 比、cAMP 和 ROS 水平）发生变化，从而进一步影响细胞命运决定。在这里，我们表明 AMPKα 和 Sir2D 是盘基网柄菌葡萄糖信号通路的组成部分，它们根据营养状况相互依赖地调节细胞代谢，并促进细胞命运决定。
