Friedreich’s ataxia (FA) is a progressive genetic disorder of the nervous system that is characterized by incoordination and cardiac degeneration. It results from the expression of a non-functional frataxin protein, which normally helps to maintain appropriate iron levels within mitochondria. The mutant protein causes cytosolic iron deficiency and mitochondrial iron overloading by methods that are not understood. Huang et al. used a conditional knockout mouse model, where frataxin was specifically deleted in only the heart and skeletal muscle, to investigate the role of frataxin in iron localization and metabolism in these tissues. Without frataxin, the expression of the iron import protein transferrin receptor 1 (TfR1) increases along with heme catabolism by heme oxygenase 1. Iron storage in cytosolic ferritin decreases and the accumulating free iron is transported into mitochondria through the transport protein mitoferrin 2 (Mfrn2), which is also upregulated in the absence of frataxin. This demonstrates a possible mechanism for the mitochondrial iron loading that underlies the pathology of Friedreich’s ataxia.

Huang ML, Becker EM, Whitnall M, Rahmanto YS, Ponka P, Richardson DR (2009). Elucidation of the mechanism of mitochondrial iron loading in Friedreich’s ataxia by analysis of a mouse mutant. Proc Natl Acad Sci USA 22, 16381– 16386.
Google Scholar
 

2009