The FOX transcription factor Hcm1 regulates oxidative metabolism in response to early nutrient limitation in yeast. Role of Snf1 and Tor1/Sch9 kinases
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2013Author
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Rodríguez Colman, Maria José;
Sorolla Bardají, Maria Alba;
Vall-llaura Espinosa, Núria;
Tamarit Sumalla, Jordi;
Ros Salvador, Joaquim;
Cabiscol Català, Elisa;
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(2013)
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The FOX transcription factor Hcm1 regulates oxidative metabolism in response to early nutrient limitation in yeast. Role of Snf1 and Tor1/Sch9 kinases.
Biochimica et Biophysica Acta, 2013, vol. 1833, núm. 8.
https://doi.org/10.1016/j.bbamcr.2013.02.015.
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Within Saccharomyces cerevisiae, Hcm1is a member of the forkhead transcription factor family with a role in
chromosome organization. Our group recently described its involvement in mitochondrial biogenesis and
stress resistance, and reports here that Hcm1 played a role in adaptation to respiratory metabolism when glucose
or nitrogen was decreased. Regulation of Hcm1 activity occurs in at least three ways: i) protein quantity,
ii) subcellular localization, and iii) transcriptional activity. Transcriptional activity was measured using a reporter
gene fused to a promoter that contains a binding site for Hcm1. We also analyzed the levels of several
genes whose expression is known to be regulated by Hcm1 levels and the role of the main kinases known to
respond to nutrients. Lack of sucrose-nonfermenting (Snf1) kinase increases cytoplasmic localization of
Hcm1, whereas Δtor1 cells showed a mild increase in nuclear Hcm1. In vitro experiments showed that Snf1
clearly phosphorylates Hcm1 while Sch9 exerts a milder phosphorylation. Although in vitroTor1 does not directly
phosphorylate Hcm1, in vivo rapamycin treatment increases nuclear Hcm1. We conclude that Hcm1
participates in the adaptation of cells from fermentation to respiratory metabolism during nutrient scarcity.
According to our hypothesis, when nutrient levels decrease, Snf1 phosphorylates Hcm1. This results in a shift
from the cytoplasm to the nucleus and increased transcriptional activity of genes involved in respiration, use
of alternative energy sources, NAD synthesis and oxidative stress resistance.