Table 2. Selected cellular functions of frataxin.

Protein	Function
Isu1/Nfs1	Scaffold proteins for Fe–S biogenesis. Frataxin controls iron entry and sulphur production through activation of cysteine desulphurization
Aconitase	FXN facilitates and stabilizes transfer of Fe group to Aconitase to convert it into its active form
Ferrochelatase	FXN meditates iron delivery to Ferrochelatase in heme synthesis
Succinate dehydrogenase	FXN regulates entry of electrons into Complex II of electron transport chain
ATP synthase	FXN regulates entry of electrons into Complex II of electron transport chain. Reduced FXN expression is correlated to a reduction in ATP
Pyruvate dehydrogenase	Pyruvate dehydrogenase subunit E3 may exhibit proteolytic activity capable of cleaving FXN under certain conditions
p38	FXN deficiency may alter p38 mitogen-activated protein kinase signaling
Nrf2	FXN deficiency impairs Nrf2 translocation to the nucleus
Nitric oxide	NO increases as a result of FXN deficiency. This increase is related to the increase in ROS due to iron accumulation. NO increases as a protective effect from Fe-mediated oxidative stress
PGC1α	PGCα is the master regulator of mitochondrial biogenesis. FXN deficiency results in dysregulation of PGC1α. This is tissue dependent but is down-regulated in most cell types
PDK1	Frataxin deficiency triggers the activation of PDK1 through increasing phosphorylation levels of S241 and may deactivate pyruvate dehydrogenase and decrease cell metabolism
Iron uptake, import, and export protein	Frataxin deficiency causes increased expression of transferrin receptor 1 and mitochondrial iron importer mitoferrin-2, and decreased expression of ferroportin1, contributing to increased iron accumulation in mitochondria

Abbreviations: Nrf2, nuclear factor E2-related factor 2, PGC1α, peroxisome proliferator-activated receptor γ coactivator 1-α.