PMT1 deficiency enhances basal UPR activity and extends replicative lifespan of Saccharomyces cerevisiae.
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.
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing, 400016, People's Republic of China.
Hong-Jing
HJ
Cui
Xin-Guang
XG
Liu
Mark
M
McCormick
Brian M
BM
Wasko
Wei
W
Zhao
Xin
X
He
Yuan
Y
Yuan
Bing-Xiong
BX
Fang
Xue-Rong
XR
Sun
Brian K
BK
Kennedy
Yousin
Y
Suh
Zhong-Jun
ZJ
Zhou
Matt
M
Kaeberlein
Wen-Li
WL
Feng
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D059865:Endoplasmic Reticulum Stress; D008136:Longevity / Q000235:genetics*; D008364:Mannosyltransferases / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response
D050976:Basic-Leucine Zipper Transcription Factors; C091341:HAC1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases