Abstract：
Metabolic enzymes can adapt during energy stress, but the consequences of these adaptations remain understudied. Here, we discovered that hexokinase 1 (HK1), a key glycolytic enzyme, forms rings around mitochondria during energy stress. These HK1-rings constrict mitochondria at contact sites with the endoplasmic reticulum (ER) and mitochondrial dynamics protein (MiD51). HK1-rings prevent mitochondrial fission by displacing the dynamin-related protein 1 (Drp1) from mitochondrial fission factor (Mff) and mitochondrial fission 1 protein (Fis1). The disassembly of HK1-rings during energy restoration correlated with mitochondrial fission. Mechanistically, we identified that the lack of ATP and glucose-6-phosphate (G6P) promotes the formation of HK1-rings. Mutations that affect the formation of HK1-rings showed that HK1-rings rewire cellular metabolism toward increased TCA cycle activity. Our findings highlight that HK1 is an energy stress sensor that regulates the shape, connectivity, and metabolic activity of mitochondria. Thus, the formation of HK1-rings may affect mitochondrial function in energy-stress-related pathologies.
摘要：
代谢酶可以在能量应激期间适应，但是这些适应的后果仍未得到充分研究。这里,我们发现己糖激酶1(HK1)，一种关键的糖酵解酶，在能量应激期间在线粒体周围形成环。这些HK1环在与内质网（ER）和线粒体动力学蛋白（MiD51）的接触部位收缩线粒体。HK1环通过从线粒体裂变因子（Mff）和线粒体裂变1蛋白（Fis1）中置换动力蛋白相关蛋白1（Drp1）来防止线粒体裂变。能量恢复过程中HK1环的分解与线粒体裂变有关。机械上,我们发现缺乏ATP和葡萄糖-6-磷酸（G6P）会促进HK1环的形成。影响HK1环形成的突变表明，HK1环将细胞代谢重新连接到增加的TCA循环活性。我们的发现强调HK1是一种能量压力传感器，可以调节形状，连通性,和线粒体的代谢活动。因此，HK1环的形成可能影响能量应激相关病理中的线粒体功能。
