Restricted glycolysis is a primary cause of the reduced growth rate of zinc-deficient yeast cells.

Autor:	MacDiarmid CW; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA. Electronic address: macdiarmid@nutrisci.wisc.edu., Taggart J; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA., Kubisiak M; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA., Eide DJ; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Apr; Vol. 300 (4), pp. 107147. Date of Electronic Publication: 2024 Mar 07.
DOI:	10.1016/j.jbc.2024.107147
Abstrakt:	Zinc is required for many critical processes, including intermediary metabolism. In Saccharomyces cerevisiae, the Zap1 activator regulates the transcription of ∼80 genes in response to Zn supply. Some Zap1-regulated genes are Zn transporters that maintain Zn homeostasis, while others mediate adaptive responses that enhance fitness. One adaptive response gene encodes the 2-cysteine peroxiredoxin Tsa1, which is critical to Zn-deficient (ZnD) growth. Depending on its redox state, Tsa1 can function as a peroxidase, a protein chaperone, or a regulatory redox sensor. In a screen for possible Tsa1 regulatory targets, we identified a mutation (cdc19 S492A ) that partially suppressed the tsa1Δ growth defect. The cdc19 S492A mutation reduced activity of its protein product, pyruvate kinase isozyme 1 (Pyk1), implicating Tsa1 in adapting glycolysis to ZnD conditions. Glycolysis requires activity of the Zn-dependent enzyme fructose-bisphosphate aldolase 1, which was substantially decreased in ZnD cells. We hypothesized that in ZnD tsa1Δ cells, the loss of a compensatory Tsa1 regulatory function causes depletion of glycolytic intermediates and restricts dependent amino acid synthesis pathways, and that the decreased activity of Pyk1 S492A counteracted this depletion by slowing the irreversible conversion of phosphoenolpyruvate to pyruvate. In support of this model, supplementing ZnD tsa1Δ cells with aromatic amino acids improved their growth. Phosphoenolpyruvate supplementation, in contrast, had a much greater effect on growth rate of WT and tsa1Δ ZnD cells, indicating that inefficient glycolysis is a major factor limiting yeast growth. Surprisingly however, this restriction was not primarily due to low fructose-bisphosphate aldolase 1 activity, but instead occurs earlier in glycolysis. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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