Premium
A pathway for assembling [4Fe‐4S] 2+ clusters in mitochondrial iron–sulfur protein biogenesis
Author(s) -
Nasta Veronica,
Suraci Dafne,
Gourdoupis Spyridon,
CiofiBaffoni Simone,
Banci Lucia
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15140
Subject(s) - biogenesis , cluster (spacecraft) , iron–sulfur cluster , chemistry , monomer , sulfur , mitochondrion , crystallography , stereochemistry , biochemistry , gene , enzyme , organic chemistry , computer science , programming language , polymer
During its late steps, the mitochondrial iron–sulfur cluster (ISC) assembly machinery leads to the formation of [4Fe‐4S] clusters. In vivo studies revealed that several proteins are implicated in the biosynthesis and trafficking of [4Fe‐4S] clusters in mitochondria. However, they do not provide a clear picture into how these proteins cooperate. Here, we showed that three late‐acting components of the mitochondrial ISC assembly machinery (GLRX5, BOLA3, and NFU1) are part of a ISC assembly pathway leading to the synthesis of a [4Fe‐4S] 2+ cluster on NFU1. We showed that the [2Fe‐2S] 2+ GLRX5‐BOLA3 complex transfers its cluster to monomeric apo NFU1 to form, in the presence of a reductant, a [4Fe‐4S] 2+ cluster bound to dimeric NFU1. The cluster formation on NFU1 does not occur with [2Fe‐2S] 2+ GLRX5, and thus, the [4Fe‐4S] cluster assembly pathway is activated only in the presence of BOLA3. These results define NFU1 as an ‘assembler’ of [4Fe‐4S] clusters, that is, a protein able of converting two [2Fe‐2S] 2+ clusters into a [4Fe‐4S] 2+ cluster. Finally, we found that the [4Fe‐4S] 2+ cluster bound to NFU1 has a coordination site which is easily accessible to sulfur‐containing ligands, as is typically observed in metallochaperones. This finding supports a role for NFU1 in promoting rapid and controlled cluster‐exchange reaction.