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Yeast YPK9 deficiency results in shortened replicative lifespan and sensitivity to hydrogen peroxide

Abstract

YPK9/YOR291W of Saccharomyces cerevisiae encodes a vacuolar membrane protein. Previous research has suggested that Ypk9p is similar to the yeast P5-type ATPase Spf1p and that it plays a role in the sequestration of heavy metals. In addition, bioinformatics analysis has suggested that Ypk9p is a homolog of human ATP13A2, which encodes a protein of the subfamily of P5 ATPases. However, no specific function of Ypk9p has been described to date. In this study, we found, for the first time, that YPK9 is involved in the oxidative stress response and modulation of the replicative lifespan (RLS). We found that YPK9 deficiency confers sensitivity to the oxidative stress inducer hydrogen peroxide accompanied by increased intracellular ROS levels, decreased mitochondrial membrane potential, abnormal mitochondrial function, and increased incidence of early apoptosis in budding yeast. More importantly, YPK9 deficiency can lead to a shortened RLS. In addition, we found that overexpression of the catalase-encoding gene CTA1 can reverse the phenotypic abnormalities of the ypk9Δ yeast strain. Collectively, these findings highlight the involvement of Ypk9p in the oxidative stress response and modulation of RLS.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

AbA:

Aureobasidin A

ATP:

Adenosine triphosphate

CHP:

Cube hydroperoxide

CLS:

Chronological life span

CR:

Caloric restriction

DAPI:

4′,6-Diamidino-2-phenilindole

DCFH-DA:

2′,7′-Dichlorofluorescein diacetate

D. melanogaster :

Drosophila melanogaster

ETC:

Electron transport chain

FITC:

Fluorescein isothiocyanate

H2O2 :

Hydrogen peroxide

LiAc:

Lithium acetate

MMP:

Mitochondrial membrane potential

mtDNA:

Mitochondrial DNA

mt-nucleoids:

Mitochondrial nucleoids

OD:

Optical density

PCR:

Polymerase chain reaction

Rh123:

Rhodamine 123

RLS:

Replicative lifespan

ROS:

Reactive oxygen species

RT-qPCR:

Real-time quantitative PCR

S. cerevisiae :

Saccharomyces cerevisiae

TBHP:

Tert-butyl hydroperoxide

TTC:

2,3,5-Triphenyltetrazolium chloride

WT:

Wild-type

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Acknowledgements

This study was supported by the China National Natural Science Foundation (Grant Nos. 31701050, 81671399, 81971329), the Natural Science Foundation of Guangdong Province (Grant No. 2018A0303070020), the Doctoral Startup Project of Guangdong medical university (Grant No. B2019039) and the Guangdong Medical Research Foundation (Grant No. 2020489). The authors are grateful to Matt Kaeberlein and Brian K. Kennedy for technical assistance.

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Xinguang Liu and Jie Ruan designed the experiments. Fang Guo, Lingyue Kong, Jiaxin Liu, Xiaoshan Hong, Zhiwen Jiang, Haochang Song and Xiaojing Cui performed experiments. Wei Zhao wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Jie Ruan or Xinguang Liu.

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Zhao, W., Guo, F., Kong, L. et al. Yeast YPK9 deficiency results in shortened replicative lifespan and sensitivity to hydrogen peroxide. Biogerontology 22, 547–563 (2021). https://doi.org/10.1007/s10522-021-09935-w

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Keywords

  • YPK9
  • Deficiency
  • Oxidative stress
  • Replicative lifespan