Reactome | Formation of 4Fe-4S cluster on ISCA1:ISCA2

Formation of 4Fe-4S cluster on ISCA1:ISCA2

Stable Identifier

R-HSA-8878815

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

ReviewStatus

5/5

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Formation of 4Fe-4S cluster on ISCA1:ISCA2

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Iron-sulfur clusters containing 4Fe-4S are assembled from 2Fe-2S clusters on ISCA1:ISCA2 heterodimers (Banci et al. 2014, Brancaccio et al. 2014, inferred from Saccharomyces cerevisiae in Mühlenhoff et al. 2011). GLRX5:2Fe-2S can donate 2Fe-2S clusters to ISCA1:ISCA2 in vitro (Banci et al. 2014, Brancaccio et al. 2014). It is unclear if other proteins also donate 2Fe-2S clusters. Two conserved C-terminal cysteines of ISCA1:ISCA2 heterodimers extract [2Fe-2S] clusters from GLRX5, forming a ISCA1:ISCA2:GLRX5 intermediate containing two 2Fe-2S clusters (Brancaccio et al. 2017). The physiological electron donor required to convert the two 2Fe-2S clusters bound to the intermediate into a 4Fe-4S cluster is not yet characterized. ISCA1, ISCA2, and IBA57 are required for formation of holoenzymes such as aconitase that contain 4Fe-4S clusters (Sheftel et al. 2012). HSCB (HSC20), the homolog of yeast JAC1, interacts with HSPA9 and appears to facilitate the reaction (Uhrigshardt et al. 2010).

Literature References

PubMed ID	Title	Journal	Year
21987576	Specialized function of yeast Isa1 and Isa2 proteins in the maturation of mitochondrial [4Fe-4S] proteins Mühlenhoff, U, Richter, N, Pines, O, Pierik, AJ, Lill, R	J. Biol. Chem.	2011
27989128	[4Fe-4S] Cluster Assembly in Mitochondria and Its Impairment by Copper Brancaccio, D, Gallo, A, Piccioli, M, Novellino, E, Ciofi-Baffoni, S, Banci, L	J. Am. Chem. Soc.	2017
25347204	Formation of [4Fe-4S] clusters in the mitochondrial iron-sulfur cluster assembly machinery Brancaccio, D, Gallo, A, Mikolajczyk, M, Zovo, K, Palumaa, P, Novellino, E, Piccioli, M, Ciofi-Baffoni, S, Banci, L	J. Am. Chem. Soc.	2014
20668094	Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron-sulfur cluster biogenesis Uhrigshardt, H, Singh, A, Kovtunovych, G, Ghosh, M, Rouault, TA	Hum. Mol. Genet.	2010
22323289	The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation Sheftel, AD, Wilbrecht, C, Stehling, O, Niggemeyer, B, Elsässer, HP, Mühlenhoff, U, Lill, R	Mol. Biol. Cell	2012
24733926	[2Fe-2S] cluster transfer in iron-sulfur protein biogenesis Banci, L, Brancaccio, D, Ciofi-Baffoni, S, Del Conte, R, Gadepalli, R, Mikolajczyk, M, Neri, S, Piccioli, M, Winkelmann, J	Proc. Natl. Acad. Sci. U.S.A.	2014