Exploring cell cycle-mediated regulations of glycolysis in budding yeast

Yanfei Zhang; Matteo Barberis

doi:10.3389/fmicb.2023.1270487

Exploring cell cycle-mediated regulations of glycolysis in budding yeast

Front Microbiol. 2023 Oct 11:14:1270487. doi: 10.3389/fmicb.2023.1270487. eCollection 2023.

Authors

Yanfei Zhang^{1

2}, Matteo Barberis^{1

2

3}

Affiliations

¹ Molecular Systems Biology, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
² Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands.
³ Centre for Mathematical and Computational Biology, CMCB, University of Surrey, Guildford, United Kingdom.

Abstract

Coordination of cell cycle with metabolism exists in all cell types that grow by division. It serves to build a new cell, (i) fueling building blocks for the synthesis of proteins, nucleic acids, and membranes, and (ii) producing energy through glycolysis. Cyclin-dependent kinases (Cdks) play an essential role in this coordination, thereby in the regulation of cell division. Cdks are functional homologs across eukaryotes and are the engines that drive cell cycle events and the clocks that time them. Their function is counteracted by stoichiometric inhibitors; specifically, inhibitors of cyclin-cyclin dependent kinase (cyclin/Cdk) complexes allow for their activity at specific times. Here, we provide a new perspective about the yet unknown cell cycle mechanisms impacting on metabolism. We first investigated the effect of the mitotic cyclin/Cdk1 complex Cyclin B/Cdk1-functional homolog in mammalian cells of the budding yeast Clb2/Cdk1-on yeast metabolic enzymes of, or related to, the glycolysis pathway. Six glycolytic enzymes (Glk1, Hxk2, Pgi1, Fba1, Tdh1, and Pgk1) were subjected to in vitro Cdk-mediated phosphorylation assays. Glucose-6-phosphate dehydrogenase (Zwf1), the first enzyme in the pentose phosphate pathway that is important for NADPH production, and 6-phospho-fructo-2-kinase (Pfk27), which catalyzes fructose-2,6-bisphosphate synthesis, a key regulator of glycolysis, were also included in the study. We found that, among these metabolic enzymes, Fba1 and Pgk1 may be phosphorylated by Cdk1, in addition to the known Cdk1-mediated phosphorylation of Gph1. We then investigated the possible effect of Sic1, stoichiometric inhibitor of mitotic cyclin/Cdk1 complexes in budding yeast, on the activities of three most relevant glycolytic enzymes: Hxk2, Glk1, and Tdh1. We found that Sic1 may have a negative effect on Hxk2. Altogether, we reveal possible new routes, to be further explored, through which cell cycle may regulate cellular metabolism. Because of the functional homology of cyclin/Cdk complexes and their stoichiometric inhibitors across evolution, our findings may be relevant for the regulation of cell division in eukaryotes.

Keywords: Sic1; cell cycle; cyclin B/Cdk1; cyclin-dependent kinase; cyclin-dependent kinase inhibitor; glycolysis; metabolic enzymes; metabolism.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Systems Biology Grant of the University of Surrey to MB, and by the SILS Starting Grant of the University of Amsterdam to MB. YZ was supported by a fellowship of the China Scholarship Council (CSC).