2024年2月5日，《自然—细胞生物学》杂志在线发表了德国科学家的一项最新研究成果。来自马克斯·普朗克衰老生物学研究所的M. Graef团队发现，Atg/ULK复合物的代谢物传感器亚基调节选择性自噬。

研究人员发现磷酸盐饥饿时，代谢物传感器Pho81通过Atg11/FIP200相互作用基团与Atg1/ULK激酶复合物（AKC）的适配亚基Atg11相互作用，从而凭借其保守的磷酸-代谢物传感SPX结构域调节自噬。值得注意的是，AKC核心部件Atg13和Atg17对于磷酸盐饥饿诱导的自噬是不可或缺的，这揭示了AKC在组成和功能上的显著可塑性。

这些数据表明，Pho81并非作为一种选择性自噬受体发挥作用，而是在磷酸盐饥饿期间通过促进Atg1磷酸化对自噬至关重要的Atg11来补偿部分失去活性的Atg13。该研究表明，Atg11/FIP200适配亚基不仅能结合选择性自噬受体，还能结合调制亚基，后者能将代谢信息直接传递给AKC以进行自噬调控。

据介绍，细胞将复杂的代谢信息转化为应激适应性自噬反应。通常，多层蛋白激酶网络汇聚到保守的AKC上，诱导非选择性和选择性形式的自噬，以应对代谢变化。

附：英文原文

Title: A metabolite sensor subunit of the Atg1/ULK complex regulates selective autophagy

Author: Gross, A. S., Ghillebert, R., Schuetter, M., Reinartz, E., Rowland, A., Bishop, B. C., Stumpe, M., Dengjel, J., Graef, M.

Issue&Volume: 2024-02-05

Abstract: Cells convert complex metabolic information into stress-adapted autophagy responses. Canonically, multilayered protein kinase networks converge on the conserved Atg1/ULK kinase complex (AKC) to induce non-selective and selective forms of autophagy in response to metabolic changes. Here we show that, upon phosphate starvation, the metabolite sensor Pho81 interacts with the adaptor subunit Atg11 at the AKC via an Atg11/FIP200 interaction motif to modulate pexophagy by virtue of its conserved phospho-metabolite sensing SPX domain. Notably, core AKC components Atg13 and Atg17 are dispensable for phosphate starvation-induced autophagy revealing significant compositional and functional plasticity of the AKC. Our data indicate that, instead of functioning as a selective autophagy receptor, Pho81 compensates for partially inactive Atg13 by promoting Atg11 phosphorylation by Atg1 critical for pexophagy during phosphate starvation. Our work shows Atg11/FIP200 adaptor subunits bind not only selective autophagy receptors but also modulator subunits that convey metabolic information directly to the AKC for autophagy regulation.

DOI: 10.1038/s41556-024-01348-4

Source: https://www.nature.com/articles/s41556-024-01348-4