Reduced Ssy1-Ptr3-Ssy5 (SPS) signaling extends replicative life span by enhancing NAD<sup>+</sup> homeostasis in Saccharomyces cerevisiae

Felicia Tsang, Christol James, Michiko Kato, Victoria Myers, Irtqa Ilyas, Matthew Tsang, Su Ju Lin

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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<sup>+</sup> 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 increasesNR salvaging. This increase contributes to NAD<sup>+</sup> homeostasis, partially ameliorating the NAD<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> metabolism, cellular life span, and diseases associated with NAD<sup>+</sup> deficiency and aging.

Original languageEnglish (US)
Pages (from-to)12753-12764
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number20
DOIs
StatePublished - May 15 2015

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NAD
Yeast
Saccharomyces cerevisiae
Homeostasis
Life Expectancy
Salvaging
Cellular Structures
Eukaryota
Pyruvic Acid
Phosphoric Monoester Hydrolases
Metabolism
Nutrients
Transcription Factors
Aging of materials
Yeasts
Phosphates
Amino Acids
Food
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Reduced Ssy1-Ptr3-Ssy5 (SPS) signaling extends replicative life span by enhancing NAD<sup>+</sup> homeostasis in Saccharomyces cerevisiae. / Tsang, Felicia; James, Christol; Kato, Michiko; Myers, Victoria; Ilyas, Irtqa; Tsang, Matthew; Lin, Su Ju.

In: Journal of Biological Chemistry, Vol. 290, No. 20, 15.05.2015, p. 12753-12764.

Research output: Contribution to journalArticle

Tsang, Felicia ; James, Christol ; Kato, Michiko ; Myers, Victoria ; Ilyas, Irtqa ; Tsang, Matthew ; Lin, Su Ju. / Reduced Ssy1-Ptr3-Ssy5 (SPS) signaling extends replicative life span by enhancing NAD<sup>+</sup> homeostasis in Saccharomyces cerevisiae. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 20. pp. 12753-12764.
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