The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability.

oleh: Tobias Wilms, Erwin Swinnen, Elja Eskes, Laura Dolz-Edo, Alice Uwineza, Ruben Van Essche, Joƫlle Rosseels, Piotr Zabrocki, Elisabetta Cameroni, Vanessa Franssens, Claudio De Virgilio, Gertien J Smits, Joris Winderickx

Format: Article
Diterbitkan: Public Library of Science (PLoS) 2017-06-01

Deskripsi

The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase) to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arises when deletion of SCH9 is combined with a dysfunctional V-ATPase, and the lack of Sch9 has a significant impact on cytosolic pH (pHc) homeostasis. Sch9 physically interacts with, and influences glucose-dependent assembly/disassembly of the V-ATPase, thereby integrating input from TORC1. Moreover, we show that the role of Sch9 in regulating ageing is tightly connected with V-ATPase activity and vacuolar acidity. As both Sch9 and the V-ATPase are highly conserved in higher eukaryotes, it will be interesting to further clarify their cooperative action on the cellular processes that influence growth and ageing.