Frataxin/FXN Protein, Human (His, Myc)

Frataxin/FXN protein serves as an activator within the core iron-sulfur cluster (ISC) assembly complex, facilitating persulfide transfer to the scaffolding protein ISCU and participating in [2Fe-2S] cluster assembly. It expedites sulfur transfer from the NFS1 persulfide intermediate to ISCU and small thiols like L-cysteine and glutathione, leading to persulfuration and sulfide release. Frataxin/FXN is integral to the de novo synthesis of a [2Fe-2S] cluster, initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) producing persulfide, which is delivered to ISCU in a FXN-dependent manner. This complex is stabilized by FDX2, providing reducing equivalents for [2Fe-2S] cluster assembly. The cluster is subsequently transferred from ISCU to chaperone proteins, including HSCB, HSPA9, and GLRX5. Frataxin/FXN may play a role in protecting against iron-catalyzed oxidative stress through its ferroxidase activity, particularly in its oligomeric form. It might also function as an iron chaperone, safeguarding the aconitase [4Fe-4S]2+ cluster and promoting enzyme reactivation. Additionally, Frataxin/FXN may act as a high-affinity iron binding partner for FECH, contributing to mitochondrial heme biosynthesis, modulating the RNA-binding activity of ACO1, and potentially influencing cytoplasmic iron-sulfur protein biogenesis, overall impacting oxidative stress resistance and cell survival.