AMPK 激活的 ULK1 磷酸化 PIKFYVE 以驱动葡萄糖饥饿期间含有 PtdIns5P 的自噬体的形成。
AMPK-activated ULK1 phosphorylates PIKFYVE to drive formation of PtdIns5P-containing autophagosomes during glucose starvation.
机构信息
Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
UK Dementia Research Institute, Cambridge, UK.
出版信息
Autophagy. 2021 Nov;17(11):3877-3878. doi: 10.1080/15548627.2021.1961409. Epub 2021 Aug 12.
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.
在葡萄糖饥饿时，会诱导巨自噬/自噬的发生，而这一过程不依赖于 PIK3C3/VPS34 复合物。最近，我们描述了一条非经典信号通路，涉及到在葡萄糖饥饿时被诱导的激酶 AMPK、ULK1 和 PIKFYVE，它们导致含有 PtdIns5P 的自噬体的形成，从而增加自噬通量并清除自噬底物。在这个级联反应中，AMPK 的激活导致 ULK1 的磷酸化。然后 ULK1 将 PIKFYVE 磷酸化在 S1548，导致其激活和增加 PtdIns5P 的形成，这使得自噬体生物发生所需的机制得以招募。
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