TOR complex 1 regulates the yeast plasma membrane proton pump and pH and potassium homeostasis

• Published in: FEBS letters 2017-07, Vol.591 (13), p.1993-2002
• Main Authors: Mahmoud, Shima, Planes, María Dolores, Cabedo, Marc, Trujillo, Cristina, Rienzo, Alessandro, Caballero‐Molada, Marcos, Sharma, Sukesh C., Montesinos, Consuelo, Mulet, José Miguel, Serrano, Ramón
• Format: Article
• Language: English
• Subjects: Biological Transport; Cell Membrane - metabolism; H+‐ATPase; Homeostasis; Hydrogen-Ion Concentration; intracellular pH; Intracellular Space - chemistry; K+ transport; Mechanistic Target of Rapamycin Complex 1; Multiprotein Complexes - metabolism; Mutation; Potassium - metabolism; Protein Phosphatase 2 - genetics; Protein Phosphatase 2 - metabolism; Proton Pumps - metabolism; Proton-Translocating ATPases - metabolism; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sit4; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.12673

We have identified in yeast a connection between two master regulators of cell growth: a biochemical connection involving the TORC1 protein kinase (which activates protein synthesis, nutrient uptake, and anabolism) and a biophysical connection involving the plasma membrane proton‐pumping H+‐ATPase Pma1 (which drives nutrient and K+ uptake and regulates pH homeostasis). Raising the temperature to nonpermissive values in a TOR thermosensitive mutant decreases Pma1 activity. Rapamycin, a TORC1 inhibitor, inhibits Pma1 dependent on its receptor Fpr1 and on the protein phosphatase Sit4, a TORC1 effector. Mutation of either Sit4 or Tco89, a nonessential subunit of TORC1, decreases proton efflux, K+ uptake, intracellular pH, cell growth, and tolerance to weak organic acids. Tco89 does not affect Pma1 activity but activates K+ transport.