Iron, Heme Synthesis and Erythropoietic Porphyrias: A Complex Interplay

Erythropoietic porphyrias are caused by enzymatic dysfunctions in the heme biosynthetic pathway, resulting in porphyrins accumulation in red blood cells. The porphyrins deposition in tissues, including the skin, leads to photosensitivity that is present in all erythropoietic porphyrias. In the bone...

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Bibliographic Details
Published in:Metabolites 2021-11, Vol.11 (12), p.798
Main Authors: Poli, Antoine, Schmitt, Caroline, Moulouel, Boualem, Mirmiran, Arienne, Puy, Hervé, Lefèbvre, Thibaud, Gouya, Laurent
Format: Article
Language:English
Subjects:
ALAS2
Anemia
Biosynthesis
Bone marrow
congenital erythropoietic porphyria
Disease
Enzymes
Erythrocytes
erythropoietic protoporphyria
Ferrochelatase
Gallbladder diseases
Gene regulation
Hematology
Heme
Hemoglobin
Intracellular
Iron
iron-sulfur cluster
Liver
Mitochondria
Mutation
Patients
Photosensitivity
Porphyrins
Post-transcription
Protoporphyrin
Protoporphyrin IX
Review
Sulfur
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Summary:Erythropoietic porphyrias are caused by enzymatic dysfunctions in the heme biosynthetic pathway, resulting in porphyrins accumulation in red blood cells. The porphyrins deposition in tissues, including the skin, leads to photosensitivity that is present in all erythropoietic porphyrias. In the bone marrow, heme synthesis is mainly controlled by intracellular labile iron by post-transcriptional regulation: translation of mRNA, the first and rate-limiting enzyme of the pathway, is inhibited when iron availability is low. Moreover, it has been shown that the expression of ferrochelatase (FECH, an iron-sulfur cluster enzyme that inserts iron into protoporphyrin IX to form heme), is regulated by intracellular iron level. Accordingly, there is accumulating evidence that iron status can mitigate disease expression in patients with erythropoietic porphyrias. This article will review the available clinical data on how iron status can modify the symptoms of erythropoietic porphyrias. We will then review the modulation of heme biosynthesis pathway by iron availability in the erythron and its role in erythropoietic porphyrias physiopathology. Finally, we will summarize what is known of FECH interactions with other proteins involved in iron metabolism in the mitochondria.
ISSN:2218-1989
2218-1989
DOI:10.3390/metabo11120798