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http://purl.uniprot.org/citations/25825491http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25825491http://www.w3.org/2000/01/rdf-schema#comment"Attenuated nutrient signaling extends the life span in yeast and higher eukaryotes; however, the mechanisms are not completely understood. Here we identify the Ssy1-Ptr3-Ssy5 (SPS) amino acid sensing pathway as a novel longevity factor. A null mutation of SSY5 (ssy5Δ) increases replicative life span (RLS) by ∼50%. Our results demonstrate that several NAD(+) homeostasis factors play key roles in this life span extension. First, expression of the putative malate-pyruvate NADH shuttle increases in ssy5Δ cells, and deleting components of this shuttle, MAE1 and OAC1, largely abolishes RLS extension. Next, we show that Stp1, a transcription factor of the SPS pathway, directly binds to the promoter of MAE1 and OAC1 to regulate their expression. Additionally, deletion of SSY5 increases nicotinamide riboside (NR) levels and phosphate-responsive (PHO) signaling activity, suggesting that ssy5Δ increases NR salvaging. This increase contributes to NAD(+) homeostasis, partially ameliorating the NAD(+) deficiency and rescuing the short life span of the npt1Δ mutant. Moreover, we observed that vacuolar phosphatase, Pho8, is partially required for ssy5Δ-mediated NR increase and RLS extension. Together, our studies present evidence that supports SPS signaling is a novel NAD(+) homeostasis factor and ssy5Δ-mediated life span extension is likely due to concomitantly increased mitochondrial and vacuolar function. Our findings may contribute to understanding the molecular basis of NAD(+) metabolism, cellular life span, and diseases associated with NAD(+) deficiency and aging."xsd:string
http://purl.uniprot.org/citations/25825491http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m115.644534"xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/author"Kato M."xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/author"Lin S.J."xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/author"Tsang M."xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/author"James C."xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/author"Tsang F."xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/author"Myers V."xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/author"Ilyas I."xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/pages"12753-12764"xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/title"Reduced Ssy1-Ptr3-Ssy5 (SPS) signaling extends replicative life span by enhancing NAD+ homeostasis in Saccharomyces cerevisiae."xsd:string
http://purl.uniprot.org/citations/25825491http://purl.uniprot.org/core/volume"290"xsd:string
http://purl.uniprot.org/citations/25825491http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25825491
http://purl.uniprot.org/citations/25825491http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25825491
http://purl.uniprot.org/uniprot/#_P11154-mappedCitation-25825491http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25825491
http://purl.uniprot.org/uniprot/#_A0A8H4FAG7-mappedCitation-25825491http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25825491
http://purl.uniprot.org/uniprot/#_A0A8H8ULB1-mappedCitation-25825491http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25825491
http://purl.uniprot.org/uniprot/#_A0A8H8UN66-mappedCitation-25825491http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25825491
http://purl.uniprot.org/uniprot/#_P41815-mappedCitation-25825491http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25825491
http://purl.uniprot.org/uniprot/#_Q03770-mappedCitation-25825491http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25825491
http://purl.uniprot.org/uniprot/#_P38084-mappedCitation-25825491http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25825491
http://purl.uniprot.org/uniprot/#_P47002-mappedCitation-25825491http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25825491