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, 37:46 | Cite as

PMT1 deficiency enhances basal UPR activity and extends replicative lifespan of Saccharomyces cerevisiae

  • Hong-Jing Cui
  • Xin-Guang Liu
  • Mark McCormick
  • Brian M. Wasko
  • Wei Zhao
  • Xin He
  • Yuan Yuan
  • Bing-Xiong Fang
  • Xue-Rong Sun
  • Brian K. Kennedy
  • Yousin Suh
  • Zhong-Jun Zhou
  • Matt Kaeberlein
  • Wen-Li Feng
Article

Abstract

Pmt1p is an important member of the protein O-mannosyltransferase (PMT) family of enzymes, which participates in the endoplasmic reticulum (ER) unfolded protein response (UPR), an important pathway for alleviating ER stress. ER stress and the UPR have been implicated in aging and age-related diseases in several organisms; however, a possible role for PMT1 in determining lifespan has not been previously described. In this study, we report that deletion of PMT1 increases replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae, while overexpression of PMT1 (PMT1-OX) reduces RLS. Relative to wild-type and PMT1-OX strains, the pmt1Δ strain had enhanced HAC1 mRNA splicing and elevated expression levels of UPR target genes. Furthermore, the increased RLS of the pmt1Δ strain could be completely abolished by deletion of either IRE1 or HAC1, two upstream modulators of the UPR. The double deletion strains pmt1Δhac1Δ and pmt1Δire1Δ also displayed generally reduced transcription of UPR target genes. Collectively, our results suggest that PMT1 deficiency enhances basal activity of the ER UPR and extends the RLS of yeast mother cells through a mechanism that requires both IRE1 and HAC1.

Keywords

Protein O-mannosyltransferase Lifespan Unfolded protein response Saccharomyces cerevisiae 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (31101051, 81170327), the Natural Science Foundation of Guangdong Province (9252402301000002), the Science & Technology Innovation Fund of Guangdong Medical College (STIF201102), and the Natural Science on the Surface of Guangdong Medical College (XK1204). This work was also supported by NIH Grant R01AG039390 to MK. MM was supported by NIH training grant T32AG000266. BMW was supported by NIH training grant T32 ES007032.

Conflict of interest

None of the authors has any conflict of interests that could affect the performance of the work or the interpretation of the data.

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Copyright information

© American Aging Association 2015

Authors and Affiliations

  • Hong-Jing Cui
    • 1
  • Xin-Guang Liu
    • 2
    • 3
  • Mark McCormick
    • 4
  • Brian M. Wasko
    • 5
  • Wei Zhao
    • 2
    • 3
  • Xin He
    • 2
    • 3
  • Yuan Yuan
    • 2
    • 3
  • Bing-Xiong Fang
    • 2
    • 3
  • Xue-Rong Sun
    • 2
    • 3
  • Brian K. Kennedy
    • 2
    • 4
  • Yousin Suh
    • 2
    • 6
  • Zhong-Jun Zhou
    • 2
    • 7
  • Matt Kaeberlein
    • 2
    • 5
  • Wen-Li Feng
    • 1
  1. 1.Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of EducationChongqing Medical UniversityChongqingPeople’s Republic of China
  2. 2.Institute of Aging ResearchGuangdong Medical CollegeDongguanPeople’s Republic of China
  3. 3.Key Laboratory for Medical Molecular Diagnostics of Guangdong ProvinceDongguanPeople’s Republic of China
  4. 4.Buck Institute for Research on AgingNovatoUSA
  5. 5.Department of PathologyUniversity of WashingtonSeattleUSA
  6. 6.Department of GeneticsAlbert Einstein College of MedicineBronxUSA
  7. 7.Department of Biochemistry, Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongHong Kong

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