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bioRxiv · 10.1101/2024.03.03.583214

The flavohemoglobin Yhb1 is a new interacting partner of the heme transporter Str3.

Lo Ying Ping, F.·Vahsen, T.·Brault, A.·Nere, R.·Labbe, S.
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Abstract

Nitric oxide (NO) is a gaseous molecule that induces nitrosative stress, which can jeopardize cell viability. Yeasts have evolved diverse detoxification mechanisms to effectively counteract NO-mediated toxicity. One mechanism relies on the flavohemoglobin Yhb1, whereas a second one requires the S-nitrosoglutathione reductase Fmd2. However, in this study, we eliminate any contribution from Fmd2 by using strains deleted for this gene. To investigate heme-dependent activation of Yhb1 in response to NO, we use hem1{Delta}-derivative Schizosaccharomyces pombe strains lacking the initial enzyme in heme biosynthesis, forcing cells to assimilate heme from external sources. Under these conditions, yhb1+ mRNA levels are repressed in the presence of iron through a mechanism involving the GATA-type transcriptional repressor Fep1. In contrast, when iron levels are low, the transcription of yhb1+is derepressed and further induced in the presence of the NO donor DETANONOate. Cells lacking Yhb1 or expressing inactive forms of Yhb1 fail to grow in a hemin-dependent manner when exposed to DETANONOate. Similarly, loss of function of the heme transporter Str3 phenocopies the effects of Yhb1 disruption by causing hypersensitivity to DETANONOate under hemin-dependent 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.

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Lo Ying Ping, F., Vahsen, T., Brault, A., Nere, R., Labbe, S.. 2024-03-04. The flavohemoglobin Yhb1 is a new interacting partner of the heme transporter Str3.. https://doi.org/10.1101/2024.03.03.583214

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