Ferrochelatase: Mapping the Intersection of Iron and Porphyrin Metabolism in the Mitochondria.

Autor:	Obi CD; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, United States., Bhuiyan T; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, United States., Dailey HA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, United States.; Department of Microbiology, University of Georgia, Athens, GA, United States., Medlock AE; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, United States.; Augusta University/University of Georgia Medical Partnership, University of Georgia, Athens, GA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 May 12; Vol. 10, pp. 894591. Date of Electronic Publication: 2022 May 12 (Print Publication: 2022).
DOI:	10.3389/fcell.2022.894591
Abstrakt:	Porphyrin and iron are ubiquitous and essential for sustaining life in virtually all living organisms. Unlike iron, which exists in many forms, porphyrin macrocycles are mostly functional as metal complexes. The iron-containing porphyrin, heme, serves as a prosthetic group in a wide array of metabolic pathways; including respiratory cytochromes, hemoglobin, cytochrome P450s, catalases, and other hemoproteins. Despite playing crucial roles in many biological processes, heme, iron, and porphyrin intermediates are potentially cytotoxic. Thus, the intersection of porphyrin and iron metabolism at heme synthesis, and intracellular trafficking of heme and its porphyrin precursors are tightly regulated processes. In this review, we discuss recent advances in understanding the physiological dynamics of eukaryotic ferrochelatase, a mitochondrially localized metalloenzyme. Ferrochelatase catalyzes the terminal step of heme biosynthesis, the insertion of ferrous iron into protoporphyrin IX to produce heme. In most eukaryotes, except plants, ferrochelatase is localized to the mitochondrial matrix, where substrates are delivered and heme is synthesized for trafficking to multiple cellular locales. Herein, we delve into the structural and functional features of ferrochelatase, as well as its metabolic regulation in the mitochondria. We discuss the regulation of ferrochelatase via post-translational modifications, transportation of substrates and product across the mitochondrial membrane, protein-protein interactions, inhibition by small-molecule inhibitors, and ferrochelatase in protozoal parasites. Overall, this review presents insight on mitochondrial heme homeostasis from the perspective of ferrochelatase. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Obi, Bhuiyan, Dailey and Medlock.)
Databáze:	MEDLINE
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