PMID- 10428860
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20220129
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 32
DP  - 1999 Aug 6
TI  - Yeast and human frataxin are processed to mature form in two sequential steps by 
      the mitochondrial processing peptidase.
PG  - 22763-9
AB  - 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.
FAU - Branda, S S
AU  - Branda SS
AD  - Department of Pediatric and Adolescent Medicine, Mayo Clinic and Foundation,
      Rochester, Minnesota 55905, USA.
FAU - Cavadini, P
AU  - Cavadini P
FAU - Adamec, J
AU  - Adamec J
FAU - Kalousek, F
AU  - Kalousek F
FAU - Taroni, F
AU  - Taroni F
FAU - Isaya, G
AU  - Isaya G
LA  - eng
GR  - E.0514/TI_/Telethon/Italy
GR  - AG15709/AG/NIA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Free Radicals)
RN  - 0 (Iron-Binding Proteins)
RN  - 0 (frataxin)
RN  - E1UOL152H7 (Iron)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.64 (mitochondrial processing peptidase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Biological Transport
MH  - Cell Compartmentation
MH  - Free Radicals/metabolism
MH  - Friedreich Ataxia/etiology
MH  - Homeostasis
MH  - Humans
MH  - Iron/metabolism
MH  - *Iron-Binding Proteins
MH  - Metalloendopeptidases/*metabolism
MH  - Molecular Sequence Data
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - *Protein Processing, Post-Translational
MH  - Saccharomyces cerevisiae
MH  - Species Specificity
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - 10.1074/jbc.274.32.22763 [doi]
AID - S0021-9258(18)81603-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 6;274(32):22763-9. doi: 10.1074/jbc.274.32.22763.