Abstract
Iron is essential for nearly all aerobic organisms. One source of iron in nature is in the form of heme. Due to its critical physiological importance as a cofactor for several enzymes, organisms have evolved various means to secure heme for their needs. In the case of heme prototrophs, these organisms possess a highly conserved eight-step biosynthetic pathway. Another means used by many organisms is to acquire heme from external sources. As opposed to the knowledge of enzymes responsible for heme biosynthesis, the nature of the players and mechanisms involved in the acquisition of exogenous heme is limited. This review focuses on a description of newly discovered proteins that have novel functions in heme assimilation in the model organism Schizosaccharomyces pombe. This tractable model allows the use of the power of genetics to selectively block heme biosynthesis, setting conditions to investigate the mechanisms by which external heme is taken up by the cells. Studies have revealed that S. pombe possesses two independent heme uptake systems that require Shu1 and Str3, respectively. Heme-bound iron is captured by Shu1 at the cell surface, triggering its internalization to the vacuole with the aid of ubiquitinated proteins and the ESCRT machinery. In the case of the plasma membrane transporter Str3, it promotes cellular heme import in cells lacking Shu1. The discovery of these two pathways may contribute to gain novel insights into the mechanisms whereby fungi assimilate heme, which is an essentially biological process for their ability to invade and colonize new niches.
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Abbreviations
- ALA:
-
δ-Aminolevulinate
- ALAD:
-
Aminolevulinic acid dehydratase
- ALAS:
-
δ-Aminolevulinic acid synthase
- CFEM:
-
Common in several fungal extracellular membrane
- ChIP:
-
Chromatin immunoprecipitation
- CME:
-
Clathrin-mediated endocytosis
- CPgenIII:
-
Coproporphyrinogen III
- CPOX:
-
Coproporphyrinogen oxidase
- ESCRT:
-
Endosomal sorting complexes required for transport
- FECH:
-
Ferrochelatase
- FeLV-C:
-
Feline leukemia virus subgroup C
- HMB:
-
Hydroxymethylbilane
- GPI:
-
Glycosylphosphatidylinositol
- ILVs:
-
Intraluminal vesicles
- MFS:
-
Major facilitator superfamily
- MVBs:
-
Multivesicular bodies
- NEAT:
-
Near-iron transporter
- PBG:
-
Porphobilinogen
- PBGD:
-
Porphobilinogen deaminase
- PPIX:
-
Protoporphyrin IX
- PPgen IX:
-
Protoporphyrinogen IX
- PPOX:
-
Protoporphyrinogen oxidase
- ROS:
-
Reactive oxygen species
- UROD:
-
Uroporphyrinogen decarboxylase
- UROgenIII:
-
Uroporphyrinogen III
- UROS:
-
Uroporphyrinogen III synthase
- ZnMP:
-
Zinc mesoporphyrin IX
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Acknowledgements
We are grateful to Dr. Gilles Dupuis for critical reading of the manuscript and for his valuable comments. T.M. and A.B. are past and current scholarship recipients, respectively, from the Fonds de Recherche du Québec (FRQ-S). This study was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC, Grant #RGPIN-2015/2020-04878) to S.L.
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Labbé, S., Mourer, T., Brault, A. et al. Machinery for fungal heme acquisition. Curr Genet 66, 703–711 (2020). https://doi.org/10.1007/s00294-020-01067-x
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DOI: https://doi.org/10.1007/s00294-020-01067-x