FXN Protein, Mouse (His)

The FXN protein operates as a pivotal activator within the core iron-sulfur cluster (ISC) assembly complex, orchestrating persulfide transfer to the scaffolding protein ISCU and participating in [2Fe-2S] cluster assembly. FXN accelerates sulfur transfer from the NFS1 persulfide intermediate to ISCU and small thiols like L-cysteine and glutathione, leading to persulfuration and eventual sulfide release. It binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly. This ISC assembly complex is integral to de novo synthesis of a [2Fe-2S] cluster, the initial step in mitochondrial iron-sulfur protein biogenesis. The process involves the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1), initiating persulfide production, and FXN-dependent delivery to ISCU. FDX2 stabilizes this complex, providing reducing equivalents for [2Fe-2S] cluster assembly. The cluster is subsequently transferred from ISCU to chaperone proteins, including HSCB, HSPA9, and GLRX5. FXN may play a role in protecting against iron-catalyzed oxidative stress by catalyzing the oxidation of Fe(2+) to Fe(3+), exhibiting ferroxidase activity in its oligomeric form. It potentially acts as an iron chaperone, safeguarding the aconitase [4Fe-4S]2+ cluster, promoting enzyme reactivation, and serving as a high-affinity iron binding partner for FECH, contributing to mitochondrial heme biosynthesis. FXN also modulates the RNA-binding activity of ACO1, may participate in cytoplasmic iron-sulfur protein biogenesis, and could contribute to oxidative stress resistance and overall cell survival.