Document Detail

Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.
MedLine Citation:
PMID:  9635427     Owner:  NLM     Status:  MEDLINE    
Hereditary spastic paraplegia (HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. We found that patients from a chromosome 16q24.3-linked HSP family are homozygous for a 9.5 kb deletion involving a gene encoding a novel protein, named Paraplegin. Two additional Paraplegin mutations, both resulting in a frameshift, were found in a complicated and in a pure form of HSP. Paraplegin is highly homologous to the yeast mitochondrial ATPases, AFG3, RCA1, and YME1, which have both proteolytic and chaperon-like activities at the inner mitochondrial membrane. Immunofluorescence analysis and import experiments showed that Paraplegin localizes to mitochondria. Analysis of muscle biopsies from two patients carrying Paraplegin mutations showed typical signs of mitochondrial OXPHOS defects, thus suggesting a mechanism for neurodegeneration in HSP-type disorders.
G Casari; M De Fusco; S Ciarmatori; M Zeviani; M Mora; P Fernandez; G De Michele; A Filla; S Cocozza; R Marconi; A Dürr; B Fontaine; A Ballabio
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  93     ISSN:  0092-8674     ISO Abbreviation:  Cell     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-07-09     Completed Date:  1998-07-09     Revised Date:  2012-02-22    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  973-83     Citation Subset:  IM    
Telethon Institute of Genetics and Medicine, Milan, Italy.
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MeSH Terms
Amino Acid Sequence
Cell Nucleus / genetics
Chromosome Deletion*
Chromosomes, Human, Pair 16 / genetics*
Cloning, Molecular
DNA, Complementary / genetics
Frameshift Mutation / genetics*
Metalloendopeptidases / genetics*
Mitochondria / enzymology
Molecular Sequence Data
Muscle, Skeletal / pathology
Oxidative Phosphorylation
RNA, Messenger / analysis
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Spastic Paraplegia, Hereditary / enzymology,  genetics*,  pathology
Yeasts / enzymology
Grant Support
767//Telethon; TGM06S01//Telethon; TGM97000//Telethon
Reg. No./Substance:
0/DNA, Complementary; 0/RNA, Messenger; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.-/SPG7 protein, human

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