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Yeasts have evolved diverse detoxification mechanisms to effectively counteract \u02d9NO\u2010mediated cytotoxicity. One mechanism relies on the flavohemoglobin Yhb1, whereas a second one requires the S\u2010nitrosoglutathione reductase Fmd2. To investigate heme\u2010dependent activation of Yhb1 in response to \u02d9NO, we use <jats:italic>hem1\u0394<\/jats:italic>\u2010derivative <jats:italic>Schizosaccharomyces pombe<\/jats:italic> strains lacking the initial enzyme in heme biosynthesis, forcing cells to assimilate heme from external sources. Under these conditions, <jats:italic>yhb1<\/jats:italic><jats:sup><jats:italic>+<\/jats:italic><\/jats:sup> mRNA levels are repressed in the presence of iron through a mechanism involving the GATA\u2010type transcriptional repressor Fep1. In contrast, when iron levels are low, the transcription of <jats:italic>yhb1<\/jats:italic><jats:sup><jats:italic>+<\/jats:italic><\/jats:sup> is derepressed and further induced in the presence of the \u02d9NO donor DETANONOate. Cells lacking Yhb1 or expressing inactive forms of Yhb1 fail to grow in a hemin\u2010dependent manner when exposed to DETANONOate. Similarly, the loss of function of the heme transporter Str3 phenocopies the effects of Yhb1 disruption by causing hypersensitivity to DETANONOate under hemin\u2010dependent culture conditions. Coimmunoprecipitation and bimolecular fluorescence complementation assays demonstrate the interaction between Yhb1 and the heme transporter Str3. Collectively, our findings unveil a novel pathway for activating Yhb1, fortifying yeast cells against nitrosative stress.<\/jats:p>","DOI":"10.1111\/mmi.15281","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T06:44:31Z","timestamp":1716446671000},"page":"29-49","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The flavohemoglobin Yhb1 is a new interacting partner of the heme transporter Str3"],"prefix":"10.1111","volume":"122","author":[{"given":"Florie Lo Ying","family":"Ping","sequence":"first","affiliation":[{"name":"D\u00e9partement de Biochimie et de G\u00e9nomique Fonctionnelle, Facult\u00e9 de m\u00e9decine et des sciences de la sant\u00e9 Universit\u00e9 de Sherbrooke  Sherbrooke Qubec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Vahsen","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie et de 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