IOP1 Protein Is an External Component of the Human Cytosolic Iron-Sulfur Cluster Assembly (CIA) Machinery and Functions in the MMS19 Protein-dependent CIA Pathway

Abstract

Background:The CIA machinery in human cells is unclear.Results: MMS19 formed a complex with MIP18, CIAO1, and IOP1, but IOP1 behaved differently from the other components. Conclusion: The CIA complex consists of a core MMS19-MIP18-CIAO1 complex, and IOP1 is an external component of the CIA machinery. Significance: This study increases the understanding of the composition of the CIA machinery in human cells and the interactions between the components.

Human CIA2A-FAM96A and CIA2B-FAM96B Integrate Iron Homeostasis and Maturation of Different Subsets of Cytosolic-Nuclear Iron-Sulfur Proteins

“…Notably, IOP1 interacts with both CIA1-CIA2A and CIA1-CIA2B-MMS19 targeting complexes (Fig. 5D) suggesting that it might be the final general CIA component acting before the branching node within the CIA machinery (Seki et al, 2013). Our present study provides a framework for future investigations on the precise molecular function of the CIA components that assist the assembly of cytosolic-nuclear Fe/S proteins in human cells.…”

“…So far, only human NBP35, IOP1 (homologue of yeast Nar1; for nomenclature see Table S1) and MMS19 have been functionally investigated, and shown to act similarly to their yeast counterparts (Gari et al, 2012; Seki et al, 2013; Song and Lee, 2008; Stehling et al, 2008; Stehling et al, 2012). Human MMS19 is specifically involved in the maturation of both DPYD and DNA polymerase POLD1, but is dispensable for IRP1 and GPAT assembly, suggesting a target-specific function of MMS19 similar to its yeast counterpart (Stehling et al, 2012).…”

The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron–sulfur proteins

“…Most of these components are essential for viability of yeast cells, and they are conserved in virtually all eukaryotes including human cells (Seki et al, 2013;Song and Lee, 2008;Stehling et al, 2008;Stehling et al, 2012;Tsaousis et al, 2014).…”

Emerging critical roles of Fe–S clusters in DNA replication and repair

“…CIA2B (FAM96B, MIP18) is the human homolog of yeast CIA2, with CIA2A (FAM96A) being a human paralog absent in yeast yet involved in cellular iron regulation via its interaction with Iron Response Protein 2 (IRP2) [211]. CIA1, CIA2-CIA2B and MMS19 have not yet been shown to hold a Fe-S cluster; it’s possible that this heterotrimer serves as a scaffold for apoproteins that in turn associates with Nar1-IOP1 to deliver one of its two Fe-S clusters [212]. …”