Autophagy induction requires the suppression of potassium influx mediated by phosphatases

Abstract

Potassium is an essential element for all living organisms. As the most abundant intracellular cation, it is vital for osmoregulation, maintenance of membrane potential, macromolecule transport and enzyme function. In this study, we identify potassium homeostasis as a previously unknown regulator of autophagy through the phosphatase activities of Ppz1 and Ppz2. We find that overexpression of either Ppz1 or Ppz2 triggers autophagy under nutrient-replete conditions, whereas the loss of both causes severe autophagy defects. Strikingly, deletion of the potassium transporters Trk1 and Trk2, which are substrates of Ppz1 and Ppz2-mediated dephosphorylation, restores autophagic activity in ppz1{Delta} ppz2{Delta} cells. Furthermore, intracellular potassium concentrations declined during autophagy induction in wild-type cells but remained stable in ppz1{Delta} ppz2{Delta} mutants. Collectively, these findings establish Ppz1 and Ppz2 as pivotal regulators of autophagy and underscore intracellular potassium reduction as a primary determinant of this process. Summary statementThis study demonstrates that potassium regulation by the phosphatases, Ppz1 and Ppz2, which suppress the major potassium transporters Trk1 and Trk2, is indispensable for autophagy induction in yeast.