Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase

Hum Mol Genet. 1998 Sep;7(9):1485-9. doi: 10.1093/hmg/7.9.1485.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • COS Cells
  • DNA Primers / genetics
  • Dimerization
  • Friedreich Ataxia / enzymology*
  • Friedreich Ataxia / genetics*
  • Gene Expression
  • Humans
  • In Vitro Techniques
  • Iron-Binding Proteins*
  • Metalloendopeptidases / chemistry
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mitochondria / enzymology
  • Mutation*
  • Phosphotransferases (Alcohol Group Acceptor) / deficiency
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Polymerase Chain Reaction
  • Protein Processing, Post-Translational
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics


  • DNA Primers
  • Iron-Binding Proteins
  • Recombinant Proteins
  • frataxin
  • Phosphotransferases (Alcohol Group Acceptor)
  • Metalloendopeptidases
  • mitochondrial processing peptidase