Cross-regulation of [2Fe-2S] cluster synthesis by ferredoxin-2 and frataxin.

ABSTRACT: Iron-sulfur (Fe-S) clusters are essential metallocofactors that perform a multitude of biological functions^1-7. Their synthesis is tightly regulated and defects in this process lead to severe diseases^8-10, such as Friedreich's ataxia, which is caused by defective expression of frataxin (FXN)¹¹. However, the underlying mechanisms that regulate this process remain unclear. Here we show that efficient Fe-S cluster assembly requires a fine-tuned balance in the ratio of FXN and ferredoxin-2 (FDX2). Fe-S clusters are assembled on the scaffold protein ISCU2; sulfur is provided as a persulfide by NFS1, and the persulfide is cleaved into sulfide by FDX2 (refs. ^12,13). FXN stimulates the whole process by accelerating the transfer of persulfide to ISCU2 (re

SUBMITTER: Want K 

PROVIDER: S-EPMC12804074 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature