Research Articles:

Advance online publication

Miguel Antunes1,2,3, Deepika Kale4, Hana Sychrová4 and Isabel Sá-Correia1,2,3

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Acetic acid-induced stress is a common challenge in natural environments and industrial bioprocesses, significantly affecting the growth and metabolic performance of Saccharomyces cerevisiae. The adaptive response and tolerance to this stress involves the activation of a complex network of molecular pathways. This study aims to delve deeper into these mechanisms in S. cerevisiae, particularly focusing on the role of the Hrk1 kinase. Hrk1 is a key determinant of acetic acid tolerance, belonging to the NPR/Hal family, whose members are implicated in the modulation of the activity of plasma membrane transporters that orchestrate nutrient uptake and ion homeostasis. The influence of Hrk1 on S. cerevisiae adaptation to acetic acid-induced stress was explored by employing a physiological approach based on previous phosphoproteomics analyses. The results from this study reflect the multifunctional roles of Hrk1 in maintaining proton and potassium homeostasis during different phases of acetic acid-stressed cultivation. Hrk1 is shown to play a role in the activation of plasma membrane H+-ATPase, maintaining pH homeostasis, and in the modulation of plasma membrane potential under acetic acid stressed cultivation. Potassium (K+) supplementation of the growth medium, particularly when provided at limiting concentrations, led to a notable improvement in acetic acid stress tolerance of the hrk1∆ strain. Moreover, abrogation of this kinase expression is shown to confer a physiological advantage to growth under K+ limitation also in the absence of acetic acid stress. The involvement of the alkali metal cation/H+ exchanger Nha1, another proposed molecular target of Hrk1, in improving yeast growth under K+ limitation or acetic acid stress, is proposed.

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ACKNOWLEDGMENTS

This work was funded by Fundação para a Ciência e a Tecnologia (FCT) through project 2022.01501.PTDC “Mechanistic insights into adaptation and increased robustness to acetic acid and other weak acids toxicity in yeasts“ and Ph.D. fellowships to MA [(FCT PhD Programme BIOTECnico (PD/BD/142944/2018 and COVID/BD/152896/2022)]. Funding received from FCT by iBB—Institute for Bioengineering and Biosciences (UIDB/04565/2020 and UIDP/04565/2020) and i4HB-Institute for Health and Bioeconomy (LA/P/0140/2020), is also acknowledged. This work was also supported by the Ministery of Education, Youth and Sport of the Czech Republic (Inter-COST LTC 20005 and LTC 20006) to H.S. This collaborative work was performed in the context of Yeast4Bio COST Action “Non-Conventional Yeasts for the Production of Bioproducts” funded by STSM grant (E-COST-GRANT-CA18229-5d162803) to MA.

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© 2019

The Hrk1 kinase is a determinant of acetic acid tolerance in yeast by modulating H+ and K+ homeostasis by Antunes et al. is licensed under a Creative Commons Attribution 4.0 International License.