Mitochondrial iron-sulfur cluster assembly (core ISC machinery)

Mitochondria build [2Fe-2S] clusters with the iron-sulfur cluster (ISC) machinery, the one function retained by every mitochondrion-related organelle, including mitosomes and hydrogenosomes that have lost respiration. This module is the eukaryote-wide core of that machinery, written so that it can be evaluated in any genome: the NFS1-ISD11 cysteine desulfurase that mobilizes sulfur; the ISCU scaffold on which the cluster is built, with frataxin as its allosteric activator; and the HSCB-mtHsp70 chaperone pair that releases the cluster to the GLRX5 carrier for delivery.

Eukaryote-wide scope comes from PAINT: the IBD nodes for Nfs1, Isd11, ISCU, frataxin, HscB, mitochondrial Hsp70 and Grx5 are all placed at Eukaryota (taxon:2759), each confirmed as an ancestor of its human representative by the node's seeds or the representative's own IBA. Read as a satisfiability rule, every part is expected in any eukaryote with a mitochondrion-related organelle, except in the lineages named below, which are not yet modelled as variants and so will be reported as assembly gaps rather than passes. The one exception checked so far: Archamoebae (Entamoeba, Mastigamoeba) replace the mitochondrial NFS1/ISCU pair with a bacterial-type NIF system (NifS/NifU), a realizer difference for the same desulfurase and scaffold activities. Other lineages use a laterally acquired SUF system, and the most reduced mitosomal lineages may lack parts of the frataxin, HSCB and GLRX5 arm, so a mitosome proteome may report gaps there that reflect the rule, not the organism. These statements come from the general literature and have not yet been checked against data in this repository. Not yet modelled: the ferredoxin electron supply (FDX2 has no review here, and FDXR's PANTHER family PTHR48467 is a broad glutamate-synthase-like family with no local PAINT data); the acyl carrier protein that binds ISD11 (NDUFAB1, no review here); the late [4Fe-4S] machinery (ISCA1, ISCA2, IBA57, NFU1, BOLA3, NUBPL); and the ABCB7/Atm1 exporter that supplies cytosolic iron-sulfur protein assembly. The Drosophila-only dmel_iron_sulfur_cluster_assembly module covers several of these and is a source for extending this rule. Selector over-matches are recorded on the Nfs1, Hsp70 and Grx5 family descriptors.