Intracellular pH conditions many cellular systems, but its mechanisms of regulation and perception are mostly unknown. We have identified two yeast genes important for tolerance to intracellular acidification caused by weak permeable acids. One corresponded to LEU2 and functions by removing the dependency of the leu2 mutant host strain on uptake of extracellular leucine. Leucine transport is inhibited by intracellular acidification, and either leucine oversupplementation or overexpression of the transporter gene BAP2 improved acid growth. Another acid-tolerance gene is GCN2, encoding a protein kinase activated by uncharged tRNAs during amino acid starvation. Gcn2 phosphorylates eIF2α (eukaryotic initiation factor 2α) (Sui2) at Ser51 and this inhibits general translation, but activates that of Gcn4, a transcription factor for amino acid biosynthetic genes. Intracellular acidification activates Gcn2 probably by inhibition of aminoacyl-tRNA synthetases because we observed accumulation of uncharged tRNAleu without leucine depletion. Gcn2 is required for leucine transport and a gcn2-null mutant is sensitive to acid stress if auxotrophic for leucine. Gcn4 is required for neither leucine transport nor acid tolerance, but a S51A sui2 mutant is acid-sensitive. This suggests that Gcn2, by phosphorylating eIF2α, may activate translation of an unknown regulator of amino acid transporters different from Gcn4.
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Research Article|
December 14 2011
A novel role for protein kinase Gcn2 in yeast tolerance to intracellular acid stress
Guillem Hueso;
Guillem Hueso
1Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-CSIC, Camino de Vera s/n, 46022 Valencia, Spain
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Rafael Aparicio-Sanchis;
Rafael Aparicio-Sanchis
1Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-CSIC, Camino de Vera s/n, 46022 Valencia, Spain
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Consuelo Montesinos;
Consuelo Montesinos
1Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-CSIC, Camino de Vera s/n, 46022 Valencia, Spain
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Silvia Lorenz;
Silvia Lorenz
1Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-CSIC, Camino de Vera s/n, 46022 Valencia, Spain
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José R. Murguía;
José R. Murguía
1Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-CSIC, Camino de Vera s/n, 46022 Valencia, Spain
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Ramón Serrano
Ramón Serrano
1
1Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-CSIC, Camino de Vera s/n, 46022 Valencia, Spain
1To whom correspondence should be addressed (email rserrano@ibmcp.upv.es).
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Publisher: Portland Press Ltd
Received:
July 14 2011
Revision Received:
September 12 2011
Accepted:
September 15 2011
Accepted Manuscript online:
September 15 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 441 (1): 255–264.
Article history
Received:
July 14 2011
Revision Received:
September 12 2011
Accepted:
September 15 2011
Accepted Manuscript online:
September 15 2011
Citation
Guillem Hueso, Rafael Aparicio-Sanchis, Consuelo Montesinos, Silvia Lorenz, José R. Murguía, Ramón Serrano; A novel role for protein kinase Gcn2 in yeast tolerance to intracellular acid stress. Biochem J 1 January 2012; 441 (1): 255–264. doi: https://doi.org/10.1042/BJ20111264
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