The Role of Sch9 and the V-ATPase in the Adaptation Response to Acetic Acid and the Consequences for Growth and Chronological Lifespan.

Marie-Anne Deprez,Lisbeth Olsson,Maurizio Bettiga,Jeroen M Maertens,Joris Winderickx

doi:10.3390/microorganisms9091871

Marie-Anne Deprez, Lisbeth Olsson + Show 3 more

Open Access

https://doi.org/10.3390/microorganisms9091871

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Journal: Microorganisms	Publication Date: Sep 3, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: KU Leuven, Chalmers University of Technology

Abstract

Studies with Saccharomyces cerevisiae indicated that non-physiologically high levels of acetic acid promote cellular acidification, chronological aging, and programmed cell death. In the current study, we compared the cellular lipid composition, acetic acid uptake, intracellular pH, growth, and chronological lifespan of wild-type cells and mutants lacking the protein kinase Sch9 and/or a functional V-ATPase when grown in medium supplemented with different acetic acid concentrations. Our data show that strains lacking the V-ATPase are especially more susceptible to growth arrest in the presence of high acetic acid concentrations, which is due to a slower adaptation to the acid stress. These V-ATPase mutants also displayed changes in lipid homeostasis, including alterations in their membrane lipid composition that influences the acetic acid diffusion rate and changes in sphingolipid metabolism and the sphingolipid rheostat, which is known to regulate stress tolerance and longevity of yeast cells. However, we provide evidence that the supplementation of 20 mM acetic acid has a cytoprotective and presumable hormesis effect that extends the longevity of all strains tested, including the V-ATPase compromised mutants. We also demonstrate that the long-lived sch9Δ strain itself secretes significant amounts of acetic acid during stationary phase, which in addition to its enhanced accumulation of storage lipids may underlie its increased lifespan.

Highlights

Weak organic acids are commonly used as preservatives due to their growth inhibiting effect, but these weak acids are produced in small amounts by yeast cells as a byproduct during fermentative growth [1]
This study demonstrated that the enhanced longevity phenotype of tor1∆ and sch9∆ strains is linked to their ability to activate an alternative metabolic pathway upon the depletion of glucose that allows to faster consume ethanol, which has pro-aging characteristics, and to utilize acetic acid for the production and storage of the protective reserve carbohydrate trehalose [38]
To identify effects of lipid metabolism and its implications for acetic acid diffusion over the plasma membranes, we performed a lipidomic shotgun analysis on WT, sch9∆, vma2∆ and sch9∆vma2∆ cells grown to mid-exponential phase on glucose-containing medium

Summary

Introduction

When yeast cells reach the diauxic shift and switch to a respiratory metabolism, acetic acid is taken up from the medium and used as a carbon source. This uptake is facilitated by the de-repression and induction of several plasma membrane acetate permeases [2,3]. Most of the acetic acid dissociates at the neutral intracellular pH (pKa 4.8), causing intracellular acidification and inhibition of fermentative enzymes, which eventually can lead to growth inhibition and even the induction of programmed cell death [5,6,7,8,9,10]. It is not the total external concentration but rather the concentration of the undissociated form of acetic acid that appears to be the main determinant for its detrimental effects on cell growth [2,11]

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