Frataxin is a mitochondrial protein deficient in Friedreich ataxia (FRDA) and 
which is associated with abnormal intramitochondrial iron handling. We 
identified the mitochondrial processing peptidase beta (MPPbeta) as a frataxin 
protein partner using the yeast two-hybrid assay. In in vitro assays, MPPbeta 
binds frataxin which is cleaved by the reconstituted MPP heterodimer. MPP 
cleavage of frataxin results in an intermediate form (amino acids 41-210) that 
is processed further to the mature form. In vitro and in vivo experiments 
suggest that two C-terminal missense mutations found in FRDA patients modulate 
interaction with MPPbeta, resulting in a slower maturation process at the normal 
cleavage site. The slower processing rate of frataxin carrying such missense 
mutations may therefore contribute to frataxin deficiency, in addition to an 
impairment of its function.