PMID- 10545606
OWN - NLM
STAT- MEDLINE
DCOM- 19991214
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 12
DP  - 1999 Nov
TI  - Maturation of frataxin within mammalian and yeast mitochondria: one-step
      processing by matrix processing peptidase.
PG  - 2255-62
AB  - Friedreich's ataxia is a neurodegenerative disease caused by mutations in the
      nuclear gene encoding frataxin (FRDA). FRDA is synthesized with an N-terminal
      signal sequence, which is removed after import into mitochondria. We have shown
      that FRDA was imported efficiently into isolated mammalian or yeast mitochondria.
      In both cases, the processing cleavage that removed the N-terminal signal
      sequence occurred in a single step on import, generating mature products of
      identical mobility. The processing cleavage could be reconstituted by incubating 
      the FRDA preprotein with rat or yeast matrix processing peptidase (MPP) expressed
      in Escherichia coli. We used these assays to evaluate the import and processing
      of an altered form of FRDA containing the disease-causing I154F mutation. No
      effects on import or maturation of this mutated FRDA were observed. Likewise, no 
      effects were observed on import and maturation of the yeast frataxin homolog
      (Yfh1p) carrying a homologous I130F mutation. These results argue against the
      possibility that the I154F mutation interferes with FRDA function via effects on 
      maturation. Other mutations can be screened for effects on FRDA biogenesis as
      described here, by evaluating import into isolated mitochondria and by testing
      maturation with purified MPP.
FAU - Gordon, D M
AU  - Gordon DM
AD  - Department of Physiology, University of Pennsylvania School of Medicine, D403
      Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
FAU - Shi, Q
AU  - Shi Q
FAU - Dancis, A
AU  - Dancis A
FAU - Pain, D
AU  - Pain D
LA  - eng
GR  - DK53953/DK/NIDDK NIH HHS/United States
GR  - GM57067/GM/NIGMS NIH HHS/United States
GR  - HL07027-24/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (DNA Primers)
RN  - 0 (Iron-Binding Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (frataxin)
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  - Animals
MH  - Base Sequence
MH  - Biological Transport
MH  - DNA Primers
MH  - Friedreich Ataxia/*metabolism
MH  - *Iron-Binding Proteins
MH  - Metalloendopeptidases/*metabolism
MH  - Mitochondria/*metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - *Protein Processing, Post-Translational
MH  - Rats
MH  - Recombinant Proteins/metabolism
MH  - Saccharomyces cerevisiae/*metabolism
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - ddc251 [pii]
AID - 10.1093/hmg/8.12.2255 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Nov;8(12):2255-62. doi: 10.1093/hmg/8.12.2255.