The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability
- Wilms, Tobias Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium
- Swinnen, Erwin Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium
- Eskes, Elja Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium
- Dolz-Edo, Laura Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands
- Uwineza, Alice Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium
- Essche, Ruben Van Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium
- Rosseels, Joëlle Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium
- Zabrocki, Piotr Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium
- Cameroni, Elisabetta Department of Biology, University of Fribourg, Switzerland
- Franssens, Vanessa Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium
- De Virgilio, Claudio Department of Biology, University of Fribourg, Switzerland
- Smits, Gertien J. Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands
- Winderickx, Joris Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium
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2017
Published in:
- PLOS Genetics. - 2017, vol. 13, no. 6, p. e1006835
English
The evolutionary conserved TOR complex 1 controls growth in response to the quality and quantity of nutrients such as carbon and amino acids. The protein kinase Sch9 is the main TORC1 effector in yeast. However, only few of its direct targets are known. In this study, we performed a genome-wide screening looking for mutants which require Sch9 function for their survival and growth. In this way, we identified multiple components of the highly conserved vacuolar proton pump (V-ATPase) which mediates the luminal acidification of multiple biosynthetic and endocytic organelles. Besides a genetic interaction, we found Sch9 also physically interacts with the V- ATPase to regulate its assembly state in response to glucose availability and TORC1 activity. Moreover, the interaction with the V-ATPase has consequences for ageing as it allowed Sch9 to control vacuolar pH and thereby trigger either lifespan extension or lifespan shortening. Hence, our results provide insights into the signaling mechanism coupling glucose availability, TORC1 signaling, pH homeostasis and longevity. As both Sch9 and the V-ATPase are highly conserved and implicated in various pathologies, these results offer fertile ground for further research in higher eukaryotes.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 305041
- DOI 10.1371/journal.pgen.1006835
- Persistent URL
- https://folia.unifr.ch/unifr/documents/306099
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