TY - JOUR
T1 - Multiple pathways regulating the calorie restriction response in yeast
AU - Rahat, Ofer
AU - Maoz, Noam
AU - Cohen, Haim Y.
N1 - Funding Information:
This study was supported by grants from the Israeli Academy of Sciences, Binational US-Israel Science Foundation, Israel Cancer Association, Koret Foundation, the Israel Cancer Research Fund, the Israel Health Ministry, and the ERC: European Research Council. O.R. is funded by the Council for Higher Education fellowship.
PY - 2011/2/1
Y1 - 2011/2/1
N2 - 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.
AB - 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.
KW - Calorie restriction
KW - Respiration
KW - Stress
KW - Yeast
UR - http://www.scopus.com/inward/record.url?scp=79951790057&partnerID=8YFLogxK
U2 - 10.1093/gerona/glq165
DO - 10.1093/gerona/glq165
M3 - Article
C2 - 21081478
AN - SCOPUS:79951790057
SN - 1079-5006
VL - 66 A
SP - 163
EP - 169
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 2
ER -