Frataxin activates mitochondrial energy conversion and oxidative phosphorylation

lFriedreich's ataxia (FA) is an autosomal recessive disease caused by decre ased expression of the mitochondrial protein frataxin, The biological funct ion of frataxin is unclear. The homologue of frataxin in yeast, YFH1, is re quired for cellular respiration and was suggested to regulate mitochondrial iron homeostasis. Patients suffering from FA exhibit decreased ATP product ion in skeletal muscle, We now demonstrate that overexpression of frataxin in mammalian cells causes a Ca2+-induced up-regulation of tricarboxylic aci d cycle flux and respiration, which, in turn, leads to an increased mitocho ndrial membrane potential (Delta Psim) and results in an elevated cellular ATP content. Thus, frataxin appears to be a key activator of mitochondrial energy conversion and oxidative phosphorylation.