Shu1 is a cell-surface protein involved in iron acquisition from heme in Schizosaccharomyces pombe.
Iron is an essential metal cofactor that is required for many biological processes. Eukaryotic cells have consequently developed different strategies for its acquisition. Until now, Schizosaccharomyces pombe was known to use reductive iron uptake and siderophore-bound iron transport to scavenge iron from the environment. Here, we report the identification of a gene designated shu1(+) that encodes a protein that enables S. pombe to take up extracellular heme for cell growth. When iron levels are low, the transcription of shu1(+) is induced, although its expression is repressed when iron levels rise. The iron-dependent down-regulation of shu1(+) requires the GATA-type transcriptional repressor Fep1, which strongly associates with a proximal promoter region of shu1(+) in vivo in response to iron repletion. HA4-tagged Shu1 localizes to the plasma membrane in cells expressing a functional shu1(+)-HA4 allele. When heme biosynthesis is selectively blocked in mutated S. pombe cells, their ability to acquire exogenous hemin or the fluorescent heme analog zinc mesoporphyrin IX is dependent on the expression of Shu1. Further analysis by absorbance spectroscopy and hemin-agarose pulldown assays showed that Shu1 interacts with hemin, with a KD of ∼2.2 μm. Taken together, results reported here revealed that S. pombe possesses an unexpected pathway for heme assimilation, which may also serve as a source of iron for cell growth.
From the Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada.
Thierry
T
Mourer
From the Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada.
Jean-François
JF
Jacques
From the Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada.
Ariane
A
Brault
From the Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada.
Martin
M
Bisaillon
From the Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada Simon.Labbe@USherbrooke.ca.
Simon
S
Labbé
D002462:Cell Membrane / Q000378:metabolism; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006418:Heme / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism; D017136:Ion Transport; D007501:Iron / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008665:Metalloporphyrins / Q000378:metabolism; D010084:Oxidation-Reduction; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
C459859:Fep1 protein, S pombe; D050980:GATA Transcription Factors; D026901:Membrane Transport Proteins; D008665:Metalloporphyrins; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D006418:Heme; D006427:Hemin; C058069:zinc mesoporphyrin; D007501:Iron
Cell-surface Protein; Heme; Iron Metabolism; Transcription Regulation; Yeast Physiology