title: Multiple pathways regulating the calorie restriction response in yeast.
abstract: In yeast, SIR2 overexpression or calorie restriction (CR) results in life-span extension. It was previously suggested that CR activates Sir2 by reducing the levels of Sir2 inhibitors, NADH, or nicotinamide. Whereas NADH reduction is associated with an increase in respiration, nicotinamide clearance is induced by the upregulation of PNC1. Here, we show that, consistent with the hormesis hypothesis, PNC1 is part of a transcriptional stress response module consisting of 39 genes that increases under various stresses. Under high CR (0.1% glucose), Pnc1 becomes activated and its levels increase. However, low CR (0.5% glucose) increases yeast life span without PNC1 induction or activation of any transcriptional stress response. Instead, microarray analysis of low CR shows that the messenger RNA levels of iron transport genes increase, suggesting that this mode of CR is regulated by a shift toward respiration and lowering NADH levels. Thus, at least two pathways regulate the CR response in yeast.
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Rahat
authors.forename: Noam
authors.initials: N
authors.lastname: Maoz
authors.forename: Haim Y
authors.initials: HY
authors.lastname: Cohen
mesh_terms: D031204:Caloric Restriction; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D008136:Longevity / Q000187:drug effects / Q000235:genetics*; D009243:NAD / Q000032:analysis / Q000378:metabolism; D009535:Nicotinamidase / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D009243:NAD; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D009535:Nicotinamidase; C474330:PNC1 protein, S cerevisiae; D005947:Glucose