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.

细胞将复杂的代谢信息转化为应激适应的自噬反应。通常，多层蛋白激酶网络汇聚在保守的 Atg1/ULK 激酶复合物 (AKC) 上，诱导非选择性和选择性形式的自噬，以响应代谢变化。在这里，我们发现，在磷酸盐饥饿时，代谢物传感器 Pho81 通过 Atg11/FIP200 相互作用基序与 AKC 上的接头亚基 Atg11 相互作用，利用其保守的磷酸代谢物传感 SPX 结构域来调节 pexophagy。值得注意的是，核心 AKC 成分 Atg13 和 Atg17 对于磷酸盐饥饿诱导的自噬是可有可无的，这揭示了 AKC 显着的组成和功能可塑性。我们的数据表明，Pho81 不是作为选择性自噬受体发挥作用，而是通过促进 Atg1 磷酸化 Atg11 来补偿部分失活的 Atg13，Atg1 对磷酸盐饥饿期间的 pexophagy 至关重要。我们的工作表明 Atg11/FIP200 衔接子亚基不仅结合选择性自噬受体，还结合调节子亚基，将代谢信息直接传递至 AKC 进行自噬调节。