Methylglyoxal Inhibits Nuclear Division Through Alterations in Vacuolar Morphology and Accumulation of Atg18 on the Vacuolar Membrane in Saccharomyces Cerevisiae

Overview

Journal Sci Rep

Specialty Science

Date 2020 Aug 19

PMID 32807835

Citations 3

Authors

Wataru Nomura

Miho Aoki

Yoshiharu Inoue

Affiliations

Soon will be listed here.

Abstract

Methylglyoxal (MG) is a natural metabolite derived from glycolysis, and it inhibits the growth of cells in all kinds of organisms. We recently reported that MG inhibits nuclear division in Saccharomyces cerevisiae. However, the mechanism by which MG blocks nuclear division remains unclear. Here, we show that increase in the levels of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P) is crucial for the inhibitory effects of MG on nuclear division, and the deletion of PtdIns(3,5)P-effector Atg18 alleviated the MG-mediated inhibitory effects. Previously, we reported that MG altered morphology of the vacuole to a single swelling form, where PtdIns(3,5)P accumulates. The changes in the vacuolar morphology were also needed by MG to exert its inhibitory effects on nuclear division. The known checkpoint machinery, including the spindle assembly checkpoint and morphological checkpoint, are not involved in the blockade of nuclear division by MG. Our results suggest that both the accumulation of Atg18 on the vacuolar membrane and alterations in vacuolar morphology are necessary for the MG-induced inhibition of nuclear division.

Citing Articles

Activation of the cell wall integrity pathway negatively regulates TORC2-Ypk1/2 signaling through blocking eisosome disassembly in Saccharomyces cerevisiae.

Nomura W, Inoue Y Commun Biol. 2024; 7(1):722.

PMID: 38862688 PMC: 11166964. DOI: 10.1038/s42003-024-06411-2.

The signalling lipid PI3,5P is essential for timely mitotic exit.

Huda M, Bektas S, Bekdas B, Caydasi A Open Biol. 2023; 13(9):230125.

PMID: 37751887 PMC: 10522413. DOI: 10.1098/rsob.230125.

Nuclear ingression of cytoplasmic bodies accompanies a boost in autophagy.

Garcia M, Kumanski S, Elias-Villalobos A, Cazevieille C, Soulet C, Moriel-Carretero M Life Sci Alliance. 2022; 5(9).

PMID: 35568434 PMC: 9107791. DOI: 10.26508/lsa.202101160.

References

Cavanaugh A, Jaspersen S . Big Lessons from Little Yeast: Budding and Fission Yeast Centrosome Structure, Duplication, and Function. Annu Rev Genet. 2017; 51:361-383. DOI: 10.1146/annurev-genet-120116-024733. View

Cid V, Jimenez J, Molina M, Sanchez M, Nombela C, Thorner J . Orchestrating the cell cycle in yeast: sequential localization of key mitotic regulators at the spindle pole and the bud neck. Microbiology (Reading). 2002; 148(Pt 9):2647-2659. DOI: 10.1099/00221287-148-9-2647. View

Inoue Y, Kimura A . Methylglyoxal and regulation of its metabolism in microorganisms. Adv Microb Physiol. 1995; 37:177-227. DOI: 10.1016/s0065-2911(08)60146-0. View

Inoue Y, Maeta K, Nomura W . Glyoxalase system in yeasts: structure, function, and physiology. Semin Cell Dev Biol. 2011; 22(3):278-84. DOI: 10.1016/j.semcdb.2011.02.002. View

Zemva J, Pfaff D, Groener J, Fleming T, Herzig S, Teleman A . Effects of the Reactive Metabolite Methylglyoxal on Cellular Signalling, Insulin Action and Metabolism - What We Know in Mammals and What We Can Learn From Yeast. Exp Clin Endocrinol Diabetes. 2018; 127(4):203-214. DOI: 10.1055/s-0043-122382. View

Tucker J, Taylor R, Christensen M, Strout C, Hanna M, Carrano A . Cytogenetic response to 1,2-dicarbonyls and hydrogen peroxide in Chinese hamster ovary AUXB1 cells and human peripheral lymphocytes. Mutat Res. 1989; 224(2):269-79. DOI: 10.1016/0165-1218(89)90166-3. View

Kani S, Nakayama E, Yoda A, Onishi N, Sougawa N, Hazaka Y . Chk2 kinase is required for methylglyoxal-induced G2/M cell-cycle checkpoint arrest: implication of cell-cycle checkpoint regulation in diabetic oxidative stress signaling. Genes Cells. 2007; 12(8):919-28. DOI: 10.1111/j.1365-2443.2007.01100.x. View

Maeta K, Izawa S, Inoue Y . Methylglyoxal, a metabolite derived from glycolysis, functions as a signal initiator of the high osmolarity glycerol-mitogen-activated protein kinase cascade and calcineurin/Crz1-mediated pathway in Saccharomyces cerevisiae. J Biol Chem. 2004; 280(1):253-60. DOI: 10.1074/jbc.M408061200. View

Nomura W, Inoue Y . Methylglyoxal activates the target of rapamycin complex 2-protein kinase C signaling pathway in Saccharomyces cerevisiae. Mol Cell Biol. 2015; 35(7):1269-80. PMC: 4355542. DOI: 10.1128/MCB.01118-14. View

10.

Nomura W, Aoki M, Inoue Y . Toxicity of dihydroxyacetone is exerted through the formation of methylglyoxal in : effects on actin polarity and nuclear division. Biochem J. 2018; 475(16):2637-2652. DOI: 10.1042/BCJ20180234. View

11.

Nomura W, Maeta K, Inoue Y . Phosphatidylinositol 3,5-bisphosphate is involved in methylglyoxal-induced activation of the Mpk1 mitogen-activated protein kinase cascade in . J Biol Chem. 2017; 292(36):15039-15048. PMC: 5592679. DOI: 10.1074/jbc.M117.791590. View

12.

McCartney A, Zhang Y, Weisman L . Phosphatidylinositol 3,5-bisphosphate: low abundance, high significance. Bioessays. 2013; 36(1):52-64. PMC: 3906640. DOI: 10.1002/bies.201300012. View

13.

Cooke F, Dove S, McEwen R, Painter G, Holmes A, Hall M . The stress-activated phosphatidylinositol 3-phosphate 5-kinase Fab1p is essential for vacuole function in S. cerevisiae. Curr Biol. 1998; 8(22):1219-22. DOI: 10.1016/s0960-9822(07)00513-1. View

14.

Gary J, Wurmser A, Bonangelino C, Weisman L, Emr S . Fab1p is essential for PtdIns(3)P 5-kinase activity and the maintenance of vacuolar size and membrane homeostasis. J Cell Biol. 1998; 143(1):65-79. PMC: 2132800. DOI: 10.1083/jcb.143.1.65. View

15.

Efe J, Botelho R, Emr S . The Fab1 phosphatidylinositol kinase pathway in the regulation of vacuole morphology. Curr Opin Cell Biol. 2005; 17(4):402-8. DOI: 10.1016/j.ceb.2005.06.002. View

16.

Li X, Wang X, Zhang X, Zhao M, Tsang W, Zhang Y . Genetically encoded fluorescent probe to visualize intracellular phosphatidylinositol 3,5-bisphosphate localization and dynamics. Proc Natl Acad Sci U S A. 2013; 110(52):21165-70. PMC: 3876232. DOI: 10.1073/pnas.1311864110. View

17.

Dove S, Dong K, Kobayashi T, Williams F, Michell R . Phosphatidylinositol 3,5-bisphosphate and Fab1p/PIKfyve underPPIn endo-lysosome function. Biochem J. 2009; 419(1):1-13. DOI: 10.1042/BJ20081950. View

18.

Bonangelino C, Nau J, Duex J, Brinkman M, Wurmser A, Gary J . Osmotic stress-induced increase of phosphatidylinositol 3,5-bisphosphate requires Vac14p, an activator of the lipid kinase Fab1p. J Cell Biol. 2002; 156(6):1015-28. PMC: 2173454. DOI: 10.1083/jcb.200201002. View

19.

Dove S, McEwen R, Mayes A, Hughes D, Beggs J, Michell R . Vac14 controls PtdIns(3,5)P(2) synthesis and Fab1-dependent protein trafficking to the multivesicular body. Curr Biol. 2002; 12(11):885-93. DOI: 10.1016/s0960-9822(02)00891-6. View

20.

Jin N, Chow C, Liu L, Zolov S, Bronson R, Davisson M . VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse. EMBO J. 2008; 27(24):3221-34. PMC: 2600653. DOI: 10.1038/emboj.2008.248. View