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PLoS Genet. 2017 Feb 23;13(2):e1006626. doi: 10.1371/journal.pgen.1006626. eCollection 2017 Feb.

Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae.

Author information

1
Ottawa Institute of Systems Biology, uOttawa, Ottawa, Ontario, Canada.
2
Department of Biochemistry, Microbiology and Immunology, uOttawa, Ottawa, Ontario, Canada.
3
Department of Cellular and Molecular Medicine, uOttawa, Ottawa, Ontario, Canada.

Abstract

Eukaryotic cells form stress granules under a variety of stresses, however the signaling pathways regulating their formation remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. Further, the Tip60 complex, the human homolog of the NuA4 complex, is required for stress granule formation in cancer cell lines. Surprisingly, the impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels, which are elevated in NuA4 mutants. While elevated acetyl-CoA levels suppress the formation of glucose-deprived stress granules, decreased acetyl-CoA levels enhance stress granule formation upon glucose deprivation. Further our work suggests that NuA4 regulates acetyl-CoA levels through the Acetyl-CoA carboxylase Acc1. Altogether this work establishes both NuA4 and the metabolite acetyl-CoA as critical signaling pathways regulating the formation of glucose-deprived stress granules.

PMID:
28231279
PMCID:
PMC5344529
DOI:
10.1371/journal.pgen.1006626
[Indexed for MEDLINE]
Free PMC Article

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