ABSTRACT

Glucose deprivation induces macroautophagy/autophagy primarily through AMPK activation. However, little is known about the exact mechanism of this signaling. A recent study from Dr. David C. Rubinsztein’s lab showed that ULK1 is activated by AMPK upon glucose starvation, resulting in the phosphorylation of the lipid kinase PIKFYVE on S1548. The activated PIKFYVE consequently enhances the formation of phosphatidylinositol-5-phosphate (PtdIns5P)-containing autophagosomes, and therefore drives autophagy upregulation. The novel discovery of how ULK1 regulates the non-canonical autophagy signaling (PtdIns5P-dependent autophagy), not only expands our knowledge of autophagy, but also sheds light on therapeutic strategies for curing human disorders, where glucose-induced starvation can play an important role.

摘要

葡萄糖剥夺主要通过 AMPK 激活诱导巨自噬/自噬。然而，关于这种信号传导的确切机制知之甚少。David C. Rubinsztein 博士实验室最近的一项研究表明，ULK1 在葡萄糖饥饿时被 AMPK 激活，导致 S1548 上的脂质激酶 PIKFYVE 磷酸化。因此，活化的 PIKFYVE 增强了含有 5-磷酸磷脂酰肌醇 (PtdIns5P) 的自噬体的形成，从而驱动自噬上调。ULK1如何调节非经典自噬信号（PtdIns5P依赖性自噬）的新发现不仅扩展了我们对自噬的认识，而且为治疗人类疾病的治疗策略提供了启示，其中葡萄糖诱导的饥饿可以发挥重要作用.