Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research, Agam-kuan, Patna, India.
Adv Parasitol. 2013;83:1-92. doi: 10.1016/B978-0-12-407705-8.00001-X.
Fe-S clusters are ensembles of sulphide-linked di-, tri-, and tetra-iron centres of a variety of metalloproteins that play important roles in reduction and oxidation of mitochondrial electron transport, energy metabolism, regulation of gene expression, cell survival, nitrogen fixation, and numerous other metabolic pathways. The Fe-S clusters are assembled by one of four distinct systems: NIF, SUF, ISC, and CIA machineries. The ISC machinery is a house-keeping system conserved widely from prokaryotes to higher eukaryotes, while the other systems are present in a limited range of organisms and play supplementary roles under certain conditions such as stress. Fe-S cluster-containing proteins and the components required for Fe-S cluster biosynthesis are modulated under stress conditions, drug resistance, and developmental stages. It is also known that a defect in Fe-S proteins and Fe-S cluster biogenesis leads to many genetic disorders in humans, which indicates the importance of the systems. In this review, we describe the biological and physiological significance of Fe-S cluster-containing proteins and their biosynthesis in parasitic protozoa including Plasmodium, Trypanosoma, Leishmania, Giardia, Trichomonas, Entamoeba, Cryptosporidium, Blastocystis, and microsporidia. We also discuss the roles of Fe-S cluster biosynthesis in proliferation, differentiation, and stress response in protozoan parasites. The heterogeneity of the systems and the compartmentalization of Fe-S cluster biogenesis in the protozoan parasites likely reflect divergent evolution under highly diverse environmental niches, and influence their parasitic lifestyle and pathogenesis. Finally, both Fe-S cluster-containing proteins and their biosynthetic machinery in protozoan parasites are remarkably different from those in their mammalian hosts. Thus, they represent a rational target for the development of novel chemotherapeutic and prophylactic agents against protozoan infections.
铁硫簇是多种金属蛋白中硫连接的二价、三价和四价铁中心的集合，在氧化还原反应、线粒体电子传递、能量代谢、基因表达调控、细胞存活、固氮以及许多其他代谢途径中发挥重要作用。铁硫簇由四个不同的系统组装而成：NIF、SUF、ISC 和 CIA 机制。ISC 机制是一种在原核生物到高等真核生物中广泛保守的管家系统，而其他系统仅存在于有限的生物体中，并在某些条件下（如应激）发挥补充作用。应激条件、耐药性和发育阶段会调节含铁硫簇的蛋白质和铁硫簇生物合成所需的成分。此外，已知铁硫蛋白和铁硫簇生物合成的缺陷会导致人类的许多遗传疾病，这表明这些系统的重要性。在这篇综述中，我们描述了铁硫簇蛋白的生物学和生理学意义及其在寄生虫原生动物中的生物合成，包括疟原虫、锥虫、利什曼原虫、贾第虫、滴虫、内阿米巴、隐孢子虫、蓝氏贾第鞭毛虫和微孢子虫。我们还讨论了铁硫簇生物合成在原生动物寄生虫增殖、分化和应激反应中的作用。这些寄生虫系统的异质性和铁硫簇生物合成的区室化可能反映了它们在高度多样化的环境小生境中的趋异进化，并影响它们的寄生生活方式和发病机制。最后，原生动物寄生虫中的铁硫簇蛋白及其生物合成机制与哺乳动物宿主中的明显不同。因此，它们是开发针对原生动物感染的新型化学治疗和预防药物的合理靶点。
