AMPK alters proteasome phosphorylation status and prevents persistent proteasome condensates

Proteasomes undergo dynamic nucleocytoplasmic translocation and phase transitions in response to glucose starvation. AMP-activated protein kinase (AMPK) is important for cytoplasmic proteasome condensate dissolution and proteasome nuclear reentry in budding yeast cells upon glucose refeeding of quiescent cells. This study demonstrates that AMPK interacts with proteasomes, and the AMPK pathway regulates proteasome phosphorylation status and condensate solubility during reversible proteasome condensate formation. AMPK and the PP1 phosphatase dynamically regulate phosphorylation of multiple proteasome subunits. Therefore, the regulation of proteasome phosphorylation by AMPK is likely to be central to proteasome biomolecular condensate formation and dissolution.蛋白酶体（Proteasomes）可响应葡萄糖饥饿条件，发生动态的核质穿梭与相变过程。AMP活化蛋白激酶（AMP-activated protein kinase, AMPK）在出芽酵母细胞中，对静息细胞复供葡萄糖后的胞质蛋白酶体凝聚体解离以及蛋白酶体的核重定位具有关键调控作用。本研究证实，AMPK可与蛋白酶体发生相互作用，且在可逆性蛋白酶体凝聚体形成过程中，AMPK信号通路可调控蛋白酶体的磷酸化状态与凝聚体溶解度。AMPK与PP1磷酸酶（PP1 phosphatase）可动态调控多种蛋白酶体亚基的磷酸化水平。因此，AMPK对蛋白酶体磷酸化的调控，大概率是蛋白酶体生物分子凝聚体形成与解离的核心调控机制。