pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity
Authors:Marie-Anne Deprez1,°, Elja Eskes1,°, Tobias Wilms1, Paula Ludovico2, Joris Winderickx1
doi: 10.15698/mic2018.03.618
Volume 5, pp. 119 to 136, published 12/01/2018.
1 Functional Biology, KU Leuven, Leuven, Belgium.
2 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal.
° Contributed equally, in alphabetical order.
Keywords:
yeast, ageing, longevity, pH, V-ATPase, Pma1, PKA, TORC1, Sch9
Corresponding Author(s):
Conflict of interest statement:
The authors report no conflict of interest. J.W. declares that he is co-founder and shareholder of the KU Leuven spin-off companies ReMYND nv (Leuven, Belgium) and ADxNeuroSciences nv (Ghent, Belgium), but this did not influence in any way the content of this manuscript, nor is there a link between the studies reported and the activities of the aforementioned companies.
Please cite this article as:
Marie-Anne Deprez, Elja Eskes, Tobias Wilms, Paula Ludovico, Joris Winderickx (2018). pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity. Microbial Cell 5(3): 119-136. doi: 10.15698/mic2018.03.618
© 2018 Deprez et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
The plasma membrane H+-ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.