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Updated: Oct 20, 2025
Studying Age-dependent Genomic Instability using the S. cerevisiae Chronological Lifespan Model
Published on: September 29, 2011
Yeast YPK9 deficiency results in shortened replicative lifespan and sensitivity to hydrogen peroxide
Wei Zhao1,2, Fang Guo1,2, Lingyue Kong1,2
1Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan, 523808, China.
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.
Insights
The yeast YPK9 gene is crucial for responding to oxidative stress and influences the cell's lifespan. Its deficiency leads to increased cell damage and a shorter replicative lifespan (RLS).
Area of Science:
- Cellular Biology
- Molecular Biology
- Genetics
Background:
- YPK9/YOR291W in Saccharomyces cerevisiae encodes a vacuolar membrane protein.
- Ypk9p is suggested to be similar to yeast P5-type ATPase Spf1p and involved in heavy metal sequestration.
- Bioinformatics suggests Ypk9p is a homolog of human ATP13A2, a P5 ATPase subfamily member.
Purpose of the Study:
- To elucidate the specific function of Ypk9p.
- To investigate the role of YPK9 in oxidative stress response and replicative lifespan (RLS).
Main Methods:
- Phenotypic analysis of YPK9 deletion (ypk9Δ) yeast strains.
- Assessment of sensitivity to hydrogen peroxide, intracellular ROS levels, mitochondrial membrane potential, and apoptosis.
- Evaluation of replicative lifespan (RLS) in YPK9 deficient yeast.
- Complementation studies by overexpressing the catalase gene CTA1.
Main Results:
- YPK9 deficiency results in sensitivity to hydrogen peroxide, increased reactive oxygen species (ROS), reduced mitochondrial membrane potential, and impaired mitochondrial function.
- ypk9Δ cells exhibit increased early apoptosis and a significantly shortened replicative lifespan (RLS).
- Overexpression of CTA1 reverses the observed phenotypic abnormalities in the ypk9Δ strain.
Conclusions:
- YPK9 plays a critical role in the oxidative stress response in budding yeast.
- YPK9 is involved in modulating the replicative lifespan (RLS) of yeast cells.
- The findings highlight Ypk9p's function in maintaining cellular homeostasis under oxidative stress.
