Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia.
The first include defects in genes directly regulating mitochondrial iron metabolism that lead to Friedreich's ataxia and the various sideroblastic anemias, with excessive mitochondrial iron accumulation.