Sulforaphane alters the acidification of the yeast vacuole

Authors:

Alexander Wilcox1,#, Michael Murphy1,#, Douglass Tucker1,#, David Laprade1, Breton Roussel1, Christopher Chin2, Victoria Hallisey1, Noah Kozub1, Abraham Brass2 and Nicanor Austriaco1

doi: 10.15698/mic2020.05.716
Volume 7, pp. 129 to 138, published 20/03/2020.

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Affiliations:

1 Department of Biology, Providence College, 1 Cunningham Square, Providence, RI 02918, USA.

2 Department of Microbiology and Physiological Systems, University of Massachusetts School of Medicine, 368 Plantation St., ASC 1001, Worcester, MA 01605, USA.

# These authors contributed equally to the manuscript.

Keywords: 

sulforaphane, yeast, vacuoles, acidification

Corresponding Author(s):

Nicanor Austriaco, Department of Biology, Providence College, 1 Cunningham Square, Providence, RI 02918, USA; naustria@providence.edu

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

Alexander Wilcox, Michael Murphy, Douglass Tucker, David Laprade, Breton Roussel, Christopher Chin, Victoria Hallisey, Noah Kozub, Abraham Brass and Nicanor Austriaco (2020). Sulforaphane alters the acidification of the yeast vacuole. Microbial Cell 7(5): 129-138. doi: 10.15698/mic2020.05.716

© 2020 Wilcox et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.

Abstract:

Sulforaphane (SFN) is a compound [1-isothiocyanato-4-(methylsulfinyl)-butane] found in broccoli and other cruciferous vegetables that is currently of interest because of its potential as a chemopreventive and a chemotherapeutic drug. Recent studies in a diverse range of cellular and animal models have shown that SFN is involved in multiple intracellular pathways that regulate xenobiotic metabolism, inflammation, cell death, cell cycle progression, and epigenetic regulation. In order to better understand the mechanisms of action behind SFN-induced cell death, we undertook an unbiased genome wide screen with the yeast knockout (YKO) library to identify SFN sensitive (SFNS) mutants. The mutants were enriched with knockouts in genes linked to vacuolar function suggesting a link between this organelle and SFN’s mechanism of action in yeast. Our subsequent work revealed that SFN increases the vacuolar pH of yeast cells and that varying the vacuolar pH can alter the sensitivity of yeast cells to the drug. In fact, several mutations that lower the vacuolar pH in yeast actually made the cells resistant to SFN (SFNR). Finally, we show that human lung cancer cells with more acidic compartments are also SFNR suggesting that SFN’s mechanism of action identified in yeast may carry over to higher eukaryotic cells.