ABSTRACT

The induction of macroautophagy/autophagy upon glucose deprivation can occur independently of the PIK3C3/VPS34 complex. Recently, we described a non-canonical signaling pathway involving the kinases AMPK, ULK1 and PIKFYVE that are induced during glucose starvation, leading to the formation of PtdIns5P-containing autophagosomes, resulting in increased autophagy flux and clearance of autophagy substrates. In this cascade, the activation of AMPK leads to ULK1 phosphorylation. ULK1 then phosphorylates PIKFYVE at S1548, leading to its activation and increased PtdIns5P formation, which enables the recruitment of machinery required for autophagosome biogenesis.

摘要

葡萄糖剥夺后巨自噬/自噬的诱导可以独立于 PIK3C3/VPS34 复合物发生。最近，我们描述了一种涉及激酶 AMPK、ULK1 和 PIKFYVE 的非经典信号通路，这些激酶在葡萄糖饥饿期间被诱导，导致含有 PtdIns5P 的自噬体的形成，导致自噬通量增加和自噬底物的清除。在这个级联中，AMPK 的激活导致 ULK1 磷酸化。然后 ULK1 在 S1548 处磷酸化 PIKFYVE，导致其活化并增加 PtdIns5P 的形成，从而能够募集自噬体生物发生所需的机制。