Iron, Heme Synthesis and Erythropoietic Porphyrias: A Complex Interplay

Metabolites

Boualem Moulouel¹  Arienne Mirmiran¹  Hervé Puy²  Laurent Gouya²  Caroline Schmitt²  Thibaud Lefèbvre²  Antoine Poli² 

[1] AP-HP, Centre Français des Porphyries, Hôpital Louis Mourier, 178 Rue des Renouillers, 92700 Colombes, France;Centre de Recherche sur L’Inflammation, Université de Paris, INSERM UMR 1149, 16 Rue Henri Huchard, 75018 Paris, France;

关键词: erythropoietic protoporphyria;    congenital erythropoietic porphyria;    ALAS2;    ferrochelatase;    iron;    iron-sulfur cluster;   

DOI  :  10.3390/metabo11120798

来源: DOAJ

【 摘 要 】

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 ALAS2 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.

【 授权许可】

Unknown