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

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

doi:10.1371/journal.pgen.1006835

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

PLoS Genet. 2017 Jun 12;13(6):e1006835. doi: 10.1371/journal.pgen.1006835. eCollection 2017 Jun.

Affiliations

¹ Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium.
² Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, GE Amsterdam, The Netherlands.
³ Department of Biology, University of Fribourg, Fribourg, Switzerland.

Abstract

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.

MeSH terms

Aging / genetics*
Glucose / metabolism*
Hydrogen-Ion Concentration
Longevity / genetics*
Protein Serine-Threonine Kinases / genetics*
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / genetics*
Signal Transduction
Transcription Factors / genetics
Vacuolar Proton-Translocating ATPases / genetics*
Vacuoles / genetics

Substances

Saccharomyces cerevisiae Proteins
TORC1 protein complex, S cerevisiae
Transcription Factors
V-ATPase a subunit, S cerevisiae
Protein Serine-Threonine Kinases
SCH9 protein, S cerevisiae
Vacuolar Proton-Translocating ATPases
Glucose

Grants and funding

Research was supported by fellowships and grants from the Instituut voor Innovatie door Wetenschap en Technologie (TW), Fonds voor Wetenschappelijk Onderzoek - Vlaanderen (ES, EE, VF, JW), KU Leuven (JW) and the canton of Fribourg and the Swiss National Science Foundation (CDV). We also thank the EC for a Marie Curie fellowship to PZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.