Yeast and human frataxin are processed to mature form in two sequential steps by the mitochondrial processing peptidase

Steven S. Branda, Patrizia Cavadini, Jiri Adamec, Frantisek Kalousek, Franco Taroni, Grazia Isaya

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Frataxin is a nuclear-encoded mitochondrial protein which is deficient in Friedreich's ataxia, a hereditary neurodegenerative disease. Yeast mutants lacking the yeast frataxin homologue (Yfh1p) show iron accumulation in mitochondria and increased sensitivity to oxidative stress, suggesting that frataxin plays a critical role in mitochondrial iron homeostasis and free radical toxicity. Both Yfh1p and frataxin are synthesized as larger precursor molecules that, upon import into mitochondria, are subject to two proteolytic cleavages, yielding an intermediate and a mature size form. A recent study found that recombinant rat mitochondrial processing peptidase (MPP) cleaves the mouse frataxin precursor to the intermediate but not the mature form (Koutnikova, H., Campuzano, V., and Koenig, M. (1998) Hum. Mol. Gen. 7, 1485- 1489), suggesting that a different peptidase might be required for production of mature size frataxin. However, in the present study we show that MPP is solely responsible for maturation of yeast and human frataxin. MPP first cleaves the precursor to intermediate form and subsequently converts the intermediate to mature size protein. In this way, MPP could influence frataxin function and indirectly affect mitochondrial iron homeostasis.

Original languageEnglish (US)
Pages (from-to)22763-22769
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number32
DOIs
StatePublished - Aug 6 1999

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Yeast
Yeasts
Mitochondria
Iron
Nervous System Heredodegenerative Disorders
Homeostasis
Neurodegenerative diseases
Friedreich Ataxia
Oxidative stress
frataxin
mitochondrial processing peptidase
Mitochondrial Proteins
Free Radicals
Toxicity
Rats
Oxidative Stress
Peptide Hydrolases
Molecules
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Yeast and human frataxin are processed to mature form in two sequential steps by the mitochondrial processing peptidase. / Branda, Steven S.; Cavadini, Patrizia; Adamec, Jiri; Kalousek, Frantisek; Taroni, Franco; Isaya, Grazia.

In: Journal of Biological Chemistry, Vol. 274, No. 32, 06.08.1999, p. 22763-22769.

Research output: Contribution to journalArticle

Branda, Steven S. ; Cavadini, Patrizia ; Adamec, Jiri ; Kalousek, Frantisek ; Taroni, Franco ; Isaya, Grazia. / Yeast and human frataxin are processed to mature form in two sequential steps by the mitochondrial processing peptidase. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 32. pp. 22763-22769.
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