Reactive oxygen species (ROS) that exceed the antioxidative capacity of the cell can be harmful and are termed oxidative stress. Increasing evidence suggests that ROS are not exclusively detrimental, but can fulfill important signaling functions. Recently, we have been able to demonstrate that a NADPH oxidase-like enzyme (termed Yno1p) exists in the single-celled organism Saccharomyces cerevisiae. This enzyme resides in the peripheral and perinuclear endoplasmic reticulum and functions in close proximity to the plasma membrane. Its product, hydrogen peroxide, which is also produced by the action of the superoxide dismutase, Sod1p, influences signaling of key regulatory proteins Ras2p and Yck1p/2p. In the present work, we demonstrate that Yno1p-derived H2O2 regulates outputs controlled by three MAP kinase pathways that can share components: the filamentous growth (filamentous growth MAPK (fMAPK)), pheromone response, and osmotic stress response (hyperosmolarity glycerol response, HOG) pathways. A key structural component and regulator in this process is the actin cytoskeleton. The nucleation and stabilization of actin are regulated by Yno1p. Cells lacking YNO1 showed reduced invasive growth, which could be reversed by stimulation of actin nucleation. Additionally, under osmotic stress, the vacuoles of a ∆yno1 strain show an enhanced fragmentation. During pheromone response induced by the addition of alpha-factor, Yno1p is responsible for a burst of ROS. Collectively, these results broaden the roles of ROS to encompass microbial differentiation responses and stress responses controlled by MAPK pathways.

Department of Biological Sciences State University of New York at Buffalo Buffalo NY 14260 1300 USA

Department of Biosciences University of Salzburg 5020 Salzburg Austria

Kent Fungal Group School of Biosciences University of Kent Kent CT2 9HY UK

Laboratory of Cell Reproduction Institute of Microbiology of the Czech Academy of Sciences Videnska 1083 142 20 Prague 4 Czech Republic

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Breitenbach M., Rinnerthaler M., Weber M., Breitenbach-Koller H., Karl T., Cullen P., Basu S., Haskova D., Hasek J. The defense and signaling role of NADPH oxidases in eukaryotic cells: Review. Wien. Med. Wochenschr. 2018;168:286–299. doi: 10.1007/s10354-018-0640-4. PubMed DOI PMC

Royer-Pokora B., Kunkel L.M., Monaco A.P., Goff S.C., Newburger P.E., Baehner R.L., Cole F.S., Curnutte J.T., Orkin S.H. Cloning the gene for an inherited human disorder—Chronic granulomatous disease—On the basis of its chromosomal location. Nature. 1986;322:32–38. doi: 10.1038/322032a0. PubMed DOI

Thomas D.C. The phagocyte respiratory burst: Historical perspectives and recent advances. Immunol. Lett. 2017;192:88–96. doi: 10.1016/j.imlet.2017.08.016. PubMed DOI

Babior B.M., Kipnes R.S., Curnutte J.T. Biological Defense Mechanisms the production by leukocytes of superoxide, a potential bactericidal agent. J. Immunol. 2014;193:5359–5362. doi: 10.1172/JCI107236. PubMed DOI

Rinnerthaler M., Buttner S., Laun P., Heeren G., Felder T.K., Klinger H., Weinberger M., Stolze K., Grousl T., Hasek J., et al. Yno1p/Aim14p, a NADPH-oxidase ortholog, controls extramitochondrial reactive oxygen species generation, apoptosis, and actin cable formation in yeast. Proc. Natl. Acad. Sci. USA. 2012;109:8658–8663. doi: 10.1073/pnas.1201629109. PubMed DOI PMC

Rossi D.C.P., Gleason J.E., Sanchez H., Schatzman S.S., Culbertson E.M., Johnson C.J., McNees C.A., Coelho C., Nett J.E., Andes D.R., et al. Candida albicans FRE8 encodes a member of the NADPH oxidase family that produces a burst of ROS during fungal morphogenesis. PLoS Pathog. 2017;13 doi: 10.1371/journal.ppat.1006763. PubMed DOI PMC

Hajjar C., Cherrier M.V., Mirandela G.D., Petit-Hartlein I., Stasia M.J., Fontecilla-Camps J.C., Fieschi F., Dupuy J. The NOX Family of Proteins Is Also Present in Bacteria. MBio. 2017;8 doi: 10.1128/mBio.01487-17. PubMed DOI PMC

Reddi A.R., Culotta V.C. SOD1 integrates signals from oxygen and glucose to repress respiration. Cell. 2013;152:224–235. doi: 10.1016/j.cell.2012.11.046. PubMed DOI PMC

Roth A.F., Papanayotou I., Davis N.G. The yeast kinase Yck2 has a tripartite palmitoylation signal. Mol. Biol. Cell. 2011;22:2702–2715. doi: 10.1091/mbc.e11-02-0115. PubMed DOI PMC

Babu P., Bryan J.D., Panek H.R., Jordan S.L., Forbrich B.M., Kelley S.C., Colvin R.T., Robinson L.C. Plasma membrane localization of the Yck2p yeast casein kinase 1 isoform requires the C-terminal extension and secretory pathway function. J. Cell Sci. 2002;115:4957–4968. doi: 10.1242/jcs.00203. PubMed DOI

Snowdon C., Johnston M. A novel role for yeast casein kinases in glucose sensing and signaling. Mol. Biol. Cell. 2016;27:3369–3375. doi: 10.1091/mbc.E16-05-0342. PubMed DOI PMC

Alvaro C.G., O’Donnell A.F., Prosser D.C., Augustine A.A., Goldman A., Brodsky J.L., Cyert M.S., Wendland B., Thorner J. Specific alpha-arrestins negatively regulate Saccharomyces cerevisiae pheromone response by down-modulating the G-protein-coupled receptor Ste2. Mol. Cell Biol. 2014;34:2660–2681. doi: 10.1128/MCB.00230-14. PubMed DOI PMC

Bartels D.J., Mitchell D.A., Dong X.W., Deschenes R.J. Erf2, a novel gene product that affects the localization and palmitoylation of Ras2 in Saccharomyces cerevisiae. Mol. Cell Biol. 1999;19:6775–6787. doi: 10.1128/MCB.19.10.6775. PubMed DOI PMC

Kim J.H., Johnston M. Two glucose-sensing pathways converge on Rgt1 to regulate expression of glucose transporter genes in Saccharomyces cerevisiae. J. Biol Chem. 2006;281:26144–26149. doi: 10.1074/jbc.M603636200. PubMed DOI

Leadsham J.E., Sanders G., Giannaki S., Bastow E.L., Hutton R., Naeimi W.R., Breitenbach M., Gourlay C.W. Loss of Cytochrome c Oxidase Promotes RAS-Dependent ROS Production from the ER Resident NADPH Oxidase, Yno1p, in Yeast. Cell Metab. 2013;18:279–286. doi: 10.1016/j.cmet.2013.07.005. PubMed DOI

Gale C.A., Bendel C.M., McClellan M., Hauser M., Becker J.M., Berman J., Hostetter M.K. Linkage of adhesion, filamentous growth, and virulence in Candida albicans to a single gene, INT1. Science. 1998;279:1355–1358. doi: 10.1126/science.279.5355.1355. PubMed DOI

Whiteway M., Bachewich C. Morphogenesis in Candida albicans. Annu. Rev. Microbiol. 2007;61:529–553. doi: 10.1146/annurev.micro.61.080706.093341. PubMed DOI PMC

Gimeno C.J., Ljungdahl P.O., Styles C.A., Fink G.R. Unipolar Cell Divisions in the Yeast Saccharomyces—Cerevisiae Lead to Filamentous Growth—Regulation by Starvation and Ras. Cell. 1992;68:1077–1090. doi: 10.1016/0092-8674(92)90079-R. PubMed DOI

Kron S.J., Styles C.A., Fink G.R. Symmetric cell division in pseudohyphae of the yeast Saccharomyces cerevisiae. Mol. Biol. Cell. 1994;5:1003–1022. doi: 10.1091/mbc.5.9.1003. PubMed DOI PMC

Cali B.M., Doyle T.C., Botstein D., Fink G.R. Multiple functions for actin during filamentous growth of Saccharomyces cerevisiae. Mol. Biol. Cell. 1998;9:1873–1889. doi: 10.1091/mbc.9.7.1873. PubMed DOI PMC

Taheri N., Kohler T., Braus G.H., Mosch H.U. Asymmetrically localized Bud8p and Bud9p proteins control yeast cell polarity and development. EMBO J. 2000;19:6686–6696. doi: 10.1093/emboj/19.24.6686. PubMed DOI PMC

Roberts R.L., Fink G.R. Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: Mating and invasive growth. Genes Dev. 1994;8:2974–2985. doi: 10.1101/gad.8.24.2974. PubMed DOI

Robertson L.S., Fink G.R. The three yeast A kinases have specific signaling functions in pseudohyphal growth. Proc. Natl. Acad. Sci. USA. 1998;95:13783–13787. doi: 10.1073/pnas.95.23.13783. PubMed DOI PMC

Lorenz M.C., Heitman J. Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog. EMBO J. 1997;16:7008–7018. doi: 10.1093/emboj/16.23.7008. PubMed DOI PMC

Pan X., Heitman J. Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Mol. Cell Biol. 1999;19:4874–4887. doi: 10.1128/MCB.19.7.4874. PubMed DOI PMC

Lamb T.M., Mitchell A.P. The transcription factor Rim101p governs ion tolerance and cell differentiation by direct repression of the regulatory genes NRG1 and SMP1 in Saccharomyces cerevisiae. Mol. Cell Biol. 2003;23:677–686. doi: 10.1128/MCB.23.2.677-686.2003. PubMed DOI PMC

Cullen P.J., Sprague G.F. The Regulation of Filamentous Growth in Yeast. Genetics. 2012;190:23–49. doi: 10.1534/genetics.111.127456. PubMed DOI PMC

Cullen P.J., Sabbagh W., Graham E., Irick M.M., van Olden E.K., Neal C., Delrow J., Bardwell L., Sprague G.F. A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast. Gene Dev. 2004;18:1695–1708. doi: 10.1101/gad.1178604. PubMed DOI PMC

Peter M., Neiman A.M., Park H.O., vanLohuizen M., Herskowitz I. Functional analysis of the interaction between the small GTP binding protein Cdc42 and the Ste20 protein kinase in yeast. EMBO J. 1996;15:7046–7059. doi: 10.1002/j.1460-2075.1996.tb01096.x. PubMed DOI PMC

Gancedo J.M. Control of pseudohyphae formation in Saccharomyces cerevisiae. FEMS Microbiol. Rev. 2001;25:107–123. doi: 10.1111/j.1574-6976.2001.tb00573.x. PubMed DOI

Mosch H.U., Roberts R.L., Fink G.R. Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA. 1996;93:5352–5356. doi: 10.1073/pnas.93.11.5352. PubMed DOI PMC

Chen R.E., Thorner J. Function and regulation in MAPK signaling pathways: Lessons learned from the yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta. 2007;1773:1311–1340. doi: 10.1016/j.bbamcr.2007.05.003. PubMed DOI PMC

Smith M.G., Swamy S.R., Pon L.A. The life cycle of actin patches in mating yeast. J. Cell Sci. 2001;114:1505–1513. PubMed

Severin F.F., Hyman A.A. Pheromone induces programmed cell death in S. cerevisiae. Curr. Biol. 2002;12:R233–235. doi: 10.1016/S0960-9822(02)00776-5. PubMed DOI

Saito H. Regulation of cross-talk in yeast MAPK signaling pathways. Curr. Opin. Microbiol. 2010;13:677–683. doi: 10.1016/j.mib.2010.09.001. PubMed DOI

Nishimura A., Yamamoto K., Oyama M., Kozuka-Hata H., Saito H., Tatebayashi K. Scaffold Protein Ahk1, Which Associates with Hkr1, Sho1, Ste11, and Pbs2, Inhibits Cross Talk Signaling from the Hkr1 Osmosensor to the Kss1 Mitogen-Activated Protein Kinase. Mol. Cell Biol. 2016;36:1109–1123. doi: 10.1128/MCB.01017-15. PubMed DOI PMC

Pitoniak A., Birkaya B., Dionne H.M., Vadaie N., Cullen P.J. The Signaling Mucins Msb2 and Hkr1 Differentially Regulate the Filamentation Mitogen-activated Protein Kinase Pathway and Contribute to a Multimodal Response. Mol. Biol. Cell. 2009;20:3101–3114. doi: 10.1091/mbc.e08-07-0760. PubMed DOI PMC

Tanaka K., Tatebayashi K., Nishimura A., Yamamoto K., Yang H.Y., Saito H. Yeast Osmosensors Hkr1 and Msb2 Activate the Hog1 MAPK Cascade by Different Mechanisms. Sci. Signal. 2014;7 doi: 10.1126/scisignal.2004780. PubMed DOI

Tatebayashi K., Tanaka K., Yang H.Y., Yamamoto K., Matsushita Y., Tomida T., Imai M., Saito H. Transmembrane mucins Hkr1 and Msb2 are putative osmosensors in the SHO1 branch of yeast HOG pathway. EMBO J. 2007;26:3521–3533. doi: 10.1038/sj.emboj.7601796. PubMed DOI PMC

Hohmann S. Osmotic stress signaling and osmoadaptation in Yeasts. Microbiol. Mol. Biol. R. 2002;66:300–372. doi: 10.1128/MMBR.66.2.300-372.2002. PubMed DOI PMC

Monteiro P.T., Oliveira J., Pais P., Antunes M., Palma M., Cavalheiro M., Galocha M., Godinho C.P., Martins L.C., Bourbon N., et al. YEASTRACT plus: A portal for cross-species comparative genomics of transcription regulation in yeasts. Nucleic Acids Res. 2020;48:D642–D649. doi: 10.1093/nar/gkz859. PubMed DOI PMC

Isgandarova S., Jones L., Forsberg D., Loncar A., Dawson J., Tedrick K., Eitzen G. Stimulation of actin polymerization by vacuoles via Cdc42p-dependent signaling. J. Biol. Chem. 2007;282:30466–30475. doi: 10.1074/jbc.M704117200. PubMed DOI

Li S.C., Kane P.M. The yeast lysosome-like vacuole: Endpoint and crossroads. BBA-Mol. Cell Res. 2009;1793:650–663. doi: 10.1016/j.bbamcr.2008.08.003. PubMed DOI PMC

Brachmann C.B., Davies A., Cost G.J., Caputo E., Li J.C., Hieter P., Boeke J.D. Designer deletion strains derived from Saccharomyces cerevisiae S288C: A useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast. 1998;14:115–132. doi: 10.1002/(SICI)1097-0061(19980130)14:2<115::AID-YEA204>3.0.CO;2-2. PubMed DOI

Van Dyk D., Pretorius I.S., Bauer F.F. Mss11p is a central element of the regulatory network that controls FLO11 expression and invasive growth in Saccharomyces cerevisiae. Genetics. 2005;169:91–106. doi: 10.1534/genetics.104.033704. PubMed DOI PMC

Klinger H., Rinnerthaler M., Lam Y.T., Laun P., Heeren G., Klocker A., Simon-Nobbe B., Dickinson J.R., Dawes I.W., Breitenbach M. Quantitation of (a)symmetric inheritance of functional and of oxidatively damaged mitochondrial aconitase in the cell division of old yeast mother cells. Exp. Gerontol. 2010;45:533–542. doi: 10.1016/j.exger.2010.03.016. PubMed DOI

Streubel M.K., Bischof J., Weiss R., Duschl J., Liedl W., Wimmer H., Breitenbach M., Weber M., Geltinger F., Richter K., et al. Behead and live long or the tale of cathepsin L. Yeast. 2018;35:237–249. doi: 10.1002/yea.3286. PubMed DOI PMC

Cullen P.J., Sprague G.F. Glucose depletion causes haploid invasive growth in yeast. Proc. Natl. Acad. Sci. USA. 2000;97:13619–13624. doi: 10.1073/pnas.240345197. PubMed DOI PMC

Zupan J., Raspor P. Quantitative agar-invasion assay. J. Microbiol. Methods. 2008;73:100–104. doi: 10.1016/j.mimet.2008.02.009. PubMed DOI

Basu S., Vadaie N., Prabhakar A., Li B., Adhikari H., Pitoniak A., Chow J., Chavel C.A., Cullen P.J. Spatial landmarks regulate a Cdc42-dependent MAPK pathway to control differentiation and the response to positional compromise. Proc. Natl. Acad. Sci. USA. 2016;113:E2019–2028. doi: 10.1073/pnas.1522679113. PubMed DOI PMC

Michaillat L., Mayer A. Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae. PLoS ONE. 2013;8:e54160. doi: 10.1371/journal.pone.0054160. PubMed DOI PMC

Heeren G., Rinnerthaler M., Laun P., von Seyerl P., Kossler S., Klinger H., Hager M., Bogengruber E., Jarolim S., Simon-Nobbe B., et al. The mitochondrial ribosomal protein of the large subunit, Afo1p, determines cellular longevity through mitochondrial back-signaling via TOR1. Aging-Us. 2009;1:622–636. doi: 10.18632/aging.100065. PubMed DOI PMC

Grant C.M., MacIver F.H., Dawes I.W. Mitochondrial function is required for resistance to oxidative stress in the yeast Saccharomyces cerevisiae. FEBS Lett. 1997;410:219–222. doi: 10.1016/S0014-5793(97)00592-9. PubMed DOI

Pyatrikas D.V., Fedoseeva I.V., Varakina N.N., Rusaleva T.M., Stepanov A.V., Fedyaeva A.V., Borovskii G.B., Rikhvanov E.G. Relation between cell death progression, reactive oxygen species production and mitochondrial membrane potential in fermenting Saccharomyces cerevisiae cells under heat-shockconditions. FEMS Microbiol. Lett. 2015;362 doi: 10.1093/femsle/fnv082. PubMed DOI

Fernandes D.C., Wosniak J., Jr., Pescatore L.A., Bertoline M.A., Liberman M., Laurindo F.R., Santos C.X. Analysis of DHE-derived oxidation products by HPLC in the assessment of superoxide production and NADPH oxidase activity in vascular systems. Am. J. Physiol. Cell Physiol. 2007;292:C413–422. doi: 10.1152/ajpcell.00188.2006. PubMed DOI

Dikalov S., Nazarewicz R., Panov A., Harrison D.G., Dikalova A. Crosstalk Between Mitochondrial ROS and NADPH Oxidases in Cardiovascular and Degenerative Diseases: Application of Mitochondria-Targeted Antioxidants. Free Radic. Bio. Med. 2011;51:S85–S86. doi: 10.1016/j.freeradbiomed.2011.10.397. DOI

Zorov D.B., Juhaszova M., Sollott S.J. Mitochondrial Reactive Oxygen Species (Ros) and Ros-Induced Ros Release. Physiol. Rev. 2014;94:909–950. doi: 10.1152/physrev.00026.2013. PubMed DOI PMC

Yi D.G., Hong S., Huh W.K. Mitochondrial dysfunction reduces yeast replicative lifespan by elevating RAS-dependent ROS production by the ER-localized NADPH oxidase Yno1. PLoS ONE. 2018;13:e0198619. doi: 10.1371/journal.pone.0198619. PubMed DOI PMC

Mateus C., Avery S.V. Destabilized green fluorescent protein for monitoring dynamic changes in yeast gene expression with flow cytometry. Yeast. 2000;16:1313–1323. doi: 10.1002/1097-0061(200010)16:14<1313::AID-YEA626>3.0.CO;2-O. PubMed DOI

Peterson J.R., Bickford L.C., Morgan D., Kim A.S., Ouerfelli O., Kirschner M.W., Rosen M.K. Chemical inhibition of N-WASP by stabilization of a native autoinhibited conformation. Nat. Struct. Mol. Biol. 2004;11:747–755. doi: 10.1038/nsmb796. PubMed DOI

Madania A., Dumoulin P., Grava S., Kitamoto H., Scharer-Brodbeck C., Soulard A., Moreau V., Winsor B. The Saccharomyces cerevisiae homologue of human Wiskott-Aldrich syndrome protein Las17p interacts with the Arp2/3 complex. Mol. Biol. Cell. 1999;10:3521–3538. doi: 10.1091/mbc.10.10.3521. PubMed DOI PMC

Aspenstrom P. The verprolin family of proteins: Regulators of cell morphogenesis and endocytosis. FEBS Lett. 2005;579:5253–5259. doi: 10.1016/j.febslet.2005.08.053. PubMed DOI

Tyler J.J., Allwood E.G., Ayscough K.R. WASP family proteins, more than Arp2/3 activators. Biochem. Soc. Trans. 2016;44:1339–1345. doi: 10.1042/BST20160176. PubMed DOI PMC

Raitt D.C., Posas F., Saito H. Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent activation of the Hog1 MAPK pathway. EMBO J. 2000;19:4623–4631. doi: 10.1093/emboj/19.17.4623. PubMed DOI PMC

Leberer E., Dignard D., Harcus D., Thomas D.Y., Whiteway M. The Protein-Kinase Homolog Ste20p Is Required to Link the Yeast Pheromone Response G-Protein Beta-Gamma Subunits to Downstream Signaling Components. EMBO J. 1992;11:4815–4824. doi: 10.1002/j.1460-2075.1992.tb05587.x. PubMed DOI PMC

Huh G.H., Damsz B., Matsumoto T.K., Reddy M.P., Rus A.M., Ibeas J.I., Narasimhan M.L., Bressan R.A., Hasegawa P.M. Salt causes ion disequilibrium-induced programmed cell death in yeast and plants. Plant J. 2002;29:649–659. doi: 10.1046/j.0960-7412.2001.01247.x. PubMed DOI

Wadskog I., Maldener C., Proksch A., Madeo F., Adler L. Yeast lacking the SRO7/SOP1-encoded tumor suppressor homologue show increased susceptibility to apoptosis-like cell death on exposure to NaCl stress. Mol. Biol. Cell. 2004;15:1436–1444. doi: 10.1091/mbc.e03-02-0114. PubMed DOI PMC

Rep M., Reiser V., Gartner U., Thevelein J.M., Hohmann S., Ammerer G., Ruis H. Osmotic stress-induced gene expression in Saccharomyces cerevisiae requires Msn1p and the novel nuclear factor Hot1p. Mol. Cell Biol. 1999;19:5474–5485. doi: 10.1128/MCB.19.8.5474. PubMed DOI PMC

Gorner W., Durchschlag E., Martinez-Pastor M.T., Estruch F., Ammerer G., Hamilton B., Ruis H., Schuller C. Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Gene Dev. 1998;12:586–597. doi: 10.1101/gad.12.4.586. PubMed DOI PMC

Berry D.B., Gasch A.P. Stress-activated Genomic Expression Changes Serve a Preparative Role for Impending Stress in Yeast. Mol. Biol. Cell. 2008;19:4580–4587. doi: 10.1091/mbc.e07-07-0680. PubMed DOI PMC

Miermont A., Waharte F., Hu S.Q., McClean M.N., Bottani S., Leon S., Hersen P. Severe osmotic compression triggers a slowdown of intracellular signaling, which can be explained by molecular crowding. Proc. Natl. Acad. Sci. USA. 2013;110:5725–5730. doi: 10.1073/pnas.1215367110. PubMed DOI PMC

Vida T.A., Emr S.D. A New Vital Stain for Visualizing Vacuolar Membrane Dynamics and Endocytosis in Yeast. J. Cell Biol. 1995;128:779–792. doi: 10.1083/jcb.128.5.779. PubMed DOI PMC

Dickinson J.R. ‘Fusel’ alcohols induce hyphal-like extensions and pseudohyphal formation in yeasts. Microbiology. 1996;142:1391–1397. doi: 10.1099/13500872-142-6-1391. PubMed DOI

Lorenz M.C., Cutler N.S., Heitman J. Characterization of alcohol-induced filamentous growth in Saccharomyces cerevisiae. Mol. Biol. Cell. 2000;11:183–199. doi: 10.1091/mbc.11.1.183. PubMed DOI PMC

Adhikari H., Cullen P.J. Metabolic Respiration Induces AMPK- and Ire1p-Dependent Activation of the p38-Type HOG MAPK Pathway. PLoS Genet. 2014;10 doi: 10.1371/journal.pgen.1004734. PubMed DOI PMC

Madhani H.D., Galitski T., Lander E.S., Fink G.R. Effectors of a developmental mitogen-activated protein kinase cascade revealed by expression signatures of signaling mutants. Proc. Natl. Acad. Sci. USA. 1999;96:12530–12535. doi: 10.1073/pnas.96.22.12530. PubMed DOI PMC

Palecek S.P., Parikh A.S., Kron S.J. Genetic analysis reveals that FLO11 upregulation and cell polarization independently regulate invasive growth in Saccharomyces cerevisiae. Genetics. 2000;156:1005–1023. PubMed PMC

Purevdorj-Gage B., Orr M.E., Stoodley P., Sheehan K.B., Hyman L.E. The role of FLO11 in Saccharomyces cerevisiae biofilm development in a laboratory based flow-cell system. FEMS Yeast Res. 2007;7:372–379. doi: 10.1111/j.1567-1364.2006.00189.x. PubMed DOI

Cullen P.J. The plate-washing assay: A simple test for filamentous growth in budding yeast. Cold Spring Harb. Protoc. 2015;2015:168–171. doi: 10.1101/pdb.prot085068. PubMed DOI PMC

Harman D. Aging: A theory based on free radical and radiation chemistry. J. Gerontol. 1956;11:298–300. doi: 10.1093/geronj/11.3.298. PubMed DOI

Schulz T.J., Zarse K., Voigt A., Urban N., Birringer M., Ristow M. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 2007;6:280–293. doi: 10.1016/j.cmet.2007.08.011. PubMed DOI

Lapointe J., Hekimi S. When a theory of aging ages badly. Cell Mol. Life Sci. 2010;67:1–8. doi: 10.1007/s00018-009-0138-8. PubMed DOI PMC

Xu N., Cheng X.X., Yu Q.L., Qian K.F., Ding X.H., Liu R.M., Zhang B., Xing L.J., Li M.C. Aft2, a Novel Transcription Regulator, Is Required for Iron Metabolism, Oxidative Stress, Surface Adhesion and Hyphal Development in Candida albicans. PLoS ONE. 2013;8 doi: 10.1371/journal.pone.0062367. PubMed DOI PMC

Zhang Y., Wang L., Liang S., Zhang P., Kang R., Zhang M., Wang M., Chen L., Yuan H., Ding S., et al. FpDep1, a component of Rpd3L histone deacetylase complex, is important for vegetative development, ROS accumulation, and pathogenesis in Fusarium pseudograminearum. Fungal Genet. Biol. 2020;135:103299. doi: 10.1016/j.fgb.2019.103299. PubMed DOI

Basso V., Znaidi S., Lagage V., Cabral V., Schoenherr F., LeibundGut-Landmann S., d’Enfert C., Bachellier-Bassi S. The two-component response regulator Skn7 belongs to a network of transcription factors regulating morphogenesis in Candida albicans and independently limits morphogenesis-induced ROS accumulation. Mol. Microbiol. 2017;106:157–182. doi: 10.1111/mmi.13758. PubMed DOI

Breitenbach M., Weber M., Rinnerthaler M., Karl T., Breitenbach-Koller L. Oxidative Stress in Fungi: Its Function in Signal Transduction, Interaction with Plant Hosts, and Lignocellulose Degradation. Biomolecules. 2015;5:318–342. doi: 10.3390/biom5020318. PubMed DOI PMC

Malagnac F., Lalucque H., Lepere G., Silar P. Two NADPH oxidase isoforms are required for sexual reproduction and ascospore germination in the filamentous fungus Podospora anserina. Fungal Genet. Biol. 2004;41:982–997. doi: 10.1016/j.fgb.2004.07.008. PubMed DOI

Lara-Ortiz T., Riveros-Rosas H., Aguirre J. Reactive oxygen species generated by microbial NADPH oxidase NoxA regulate sexual development in Aspergillus nidulans. Mol. Microbiol. 2003;50:1241–1255. doi: 10.1046/j.1365-2958.2003.03800.x. PubMed DOI

Cano-Dominguez N., Alvarez-Delfin K., Hansberg W., Aguirre J. NADPH oxidases NOX-1 and NOX-2 require the regulatory subunit NOR-1 to control cell differentiation and growth in Neurospora crassa. Eukaryot. Cell. 2008;7:1352–1361. doi: 10.1128/EC.00137-08. PubMed DOI PMC

Kayano Y., Tanaka A., Akano F., Scott B., Takemoto D. Differential roles of NADPH oxidases and associated regulators in polarized growth, conidiation and hyphal fusion in the symbiotic fungus Epichloe festucae. Fungal Genet. Biol. 2013;56:87–97. doi: 10.1016/j.fgb.2013.05.001. PubMed DOI

Costanzo M., Baryshnikova A., Bellay J., Kim Y., Spear E.D., Sevier C.S., Ding H., Koh J.L., Toufighi K., Mostafavi S., et al. The genetic landscape of a cell. Science. 2010;327:425–431. doi: 10.1126/science.1180823. PubMed DOI PMC

Costanzo M., VanderSluis B., Koch E.N., Baryshnikova A., Pons C., Tan G., Wang W., Usaj M., Hanchard J., Lee S.D., et al. A global genetic interaction network maps a wiring diagram of cellular function. Science. 2016;353 doi: 10.1126/science.aaf1420. PubMed DOI PMC

Sharifpoor S., van Dyk D., Costanzo M., Baryshnikova A., Friesen H., Douglas A.C., Youn J.Y., VanderSluis B., Myers C.L., Papp B., et al. Functional wiring of the yeast kinome revealed by global analysis of genetic network motifs. Genome Res. 2012;22:791–801. doi: 10.1101/gr.129213.111. PubMed DOI PMC

Perez P., Rincon S.A. Rho GTPases: Regulation of cell polarity and growth in yeasts. Biochem. J. 2010;426:243–253. doi: 10.1042/BJ20091823. PubMed DOI

Evangelista M., Klebl B.M., Tong A.H.Y., Webb B.A., Leeuw T., Leberer E., Whiteway M., Thomas D.Y., Boone C. A role for myosin-I in actin assembly through interactions with Vrp1p, Bee1p, and the Arp2/3 complex. J. Cell Biol. 2000;148:353–362. doi: 10.1083/jcb.148.2.353. PubMed DOI PMC

Tedrick K., Trischuk T., Lehner R., Eitzen G. Enhanced membrane fusion in sterol-enriched vacuoles bypasses the Vrp1p requirement. Mol. Biol. Cell. 2004;15:4609–4621. doi: 10.1091/mbc.e04-03-0194. PubMed DOI PMC

Montllor-Albalate C., Colin A.E., Chandrasekharan B., Bolaji N., Andersen J.L., Outten F.W., Reddi A.R. Extra-mitochondrial Cu/Zn superoxide dismutase (Sod1) is dispensable for protection against oxidative stress but mediates peroxide signaling in Saccharomyces cerevisiae. Redox Biol. 2019;21 doi: 10.1016/j.redox.2018.11.022. PubMed DOI PMC

Martiniere A., Fiche J.B., Smokvarska M., Mari S., Alcon C., Dumont X., Hematy K., Jaillais Y., Nollmann M., Maurel C. Osmotic Stress Activates Two Reactive Oxygen Species Pathways with Distinct Effects on Protein Nanodomains and Diffusion. Plant Physiol. 2019;179:1581–1593. doi: 10.1104/pp.18.01065. PubMed DOI PMC

Farah M.E., Sirotkin V., Haarer B., Kakhniashvili D., Amberg D.C. Diverse protective roles of the actin cytoskeleton during oxidative stress. Cytoskeleton. 2011;68:340–354. doi: 10.1002/cm.20516. PubMed DOI PMC

Carmona-Gutierrez D., Eisenberg T., Buttner S., Meisinger C., Kroemer G., Madeo F. Apoptosis in yeast: Triggers, pathways, subroutines. Cell Death Differ. 2010;17:763–773. doi: 10.1038/cdd.2009.219. PubMed DOI

Perrone G.G., Tan S.X., Dawes I.W. Reactive oxygen species and yeast apoptosis. Biochim. Biophys. Acta. 2008;1783:1354–1368. doi: 10.1016/j.bbamcr.2008.01.023. PubMed DOI

Karpova T.S., McNally J.G., Moltz S.L., Cooper J.A. Assembly and function of the actin cytoskeleton of yeast: Relationships between cables and patches. J. Cell Biol. 1998;142:1501–1517. doi: 10.1083/jcb.142.6.1501. PubMed DOI PMC

Chowdhury S., Smith K.W., Gustin M.C. Osmotic stress and the yeast cytoskeleton: Phenotype-specific suppression of an actin mutation. J. Cell Biol. 1992;118:561–571. doi: 10.1083/jcb.118.3.561. PubMed DOI PMC

Lechler T., Jonsdottir G.A., Klee S.K., Pellman D., Li R. A two-tiered mechanism by which Cdc42 controls the localization and activation of an Arp2/3-activating motor complex in yeast. J. Cell Biol. 2001;155:261–270. doi: 10.1083/jcb.200104094. PubMed DOI PMC