Functional and genomic analysis of the human mitochondrial intermediate peptidase, a putative protein partner of frataxin

Anne Chew, Giorgio Sirugo, John P. Alsobrook, Grazia Isaya

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We showed recently that the yeast mitochondrial intermediate peptidase (YMIP polypeptide; gene symbol, OCT1) promotes mitochondrial iron uptake by catalyzing the maturation of iron-utilizing proteins and exacerbates the mitochondrial iron accumulation that results from loss of yeast frataxin, a mitochondrial protein required for mitochondrial iron efflux. This suggests that the human MIP (HMIP polypeptide; gene symbol MIPEP) may be one or the loci predicted to influence the clinical manifestations of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by lack of human frataxin. To begin to test this hypothesis, we have characterized HMIP at the functional and genomic levels. We show that HMIP can complement a yeast knock-out mutant lacking. YMIP, demonstrating that HMIP and YMIP are functional homologues. The MIPEP gene spans 57 kb and consists of 19 exons that correlate with the functional domains of HMIP. Primer analysis has identified major transcript of extension the MIPEP gene expressed differentially and predominantly in tissues with high oxygen consumption, while sequence analysis of ~2 kb of 5'-flanking DNA has revealed putative Mt1/3/4, NF-κB, and AP-1 elements that may regulate MIPEP expression in these tissues. Using a new polymorphic (CA), repeat in intron 4, MIPEP has been genetically mapped within a 7-cM interval between markers D13S283 and D13S217 on 13q12. This work provides the basis for molecular analysis of MIPEP in FRDA and possibly other neurodegenerative diseases. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)104-112
Number of pages9
JournalGenomics
Volume65
Issue number2
DOIs
StatePublished - Apr 15 2000

Fingerprint

Iron
Friedreich Ataxia
Yeasts
Mitochondrial Proteins
Neurodegenerative Diseases
Genes
Proteins
Peptides
Transcription Factor AP-1
Oxygen Consumption
Introns
Sequence Analysis
Exons
mitochondrial intermediate peptidase
frataxin
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

Functional and genomic analysis of the human mitochondrial intermediate peptidase, a putative protein partner of frataxin. / Chew, Anne; Sirugo, Giorgio; Alsobrook, John P.; Isaya, Grazia.

In: Genomics, Vol. 65, No. 2, 15.04.2000, p. 104-112.

Research output: Contribution to journalArticle

Chew, Anne ; Sirugo, Giorgio ; Alsobrook, John P. ; Isaya, Grazia. / Functional and genomic analysis of the human mitochondrial intermediate peptidase, a putative protein partner of frataxin. In: Genomics. 2000 ; Vol. 65, No. 2. pp. 104-112.
@article{5b1e492cf3c3417eb533739ab163dfd2,
title = "Functional and genomic analysis of the human mitochondrial intermediate peptidase, a putative protein partner of frataxin",
abstract = "We showed recently that the yeast mitochondrial intermediate peptidase (YMIP polypeptide; gene symbol, OCT1) promotes mitochondrial iron uptake by catalyzing the maturation of iron-utilizing proteins and exacerbates the mitochondrial iron accumulation that results from loss of yeast frataxin, a mitochondrial protein required for mitochondrial iron efflux. This suggests that the human MIP (HMIP polypeptide; gene symbol MIPEP) may be one or the loci predicted to influence the clinical manifestations of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by lack of human frataxin. To begin to test this hypothesis, we have characterized HMIP at the functional and genomic levels. We show that HMIP can complement a yeast knock-out mutant lacking. YMIP, demonstrating that HMIP and YMIP are functional homologues. The MIPEP gene spans 57 kb and consists of 19 exons that correlate with the functional domains of HMIP. Primer analysis has identified major transcript of extension the MIPEP gene expressed differentially and predominantly in tissues with high oxygen consumption, while sequence analysis of ~2 kb of 5'-flanking DNA has revealed putative Mt1/3/4, NF-κB, and AP-1 elements that may regulate MIPEP expression in these tissues. Using a new polymorphic (CA), repeat in intron 4, MIPEP has been genetically mapped within a 7-cM interval between markers D13S283 and D13S217 on 13q12. This work provides the basis for molecular analysis of MIPEP in FRDA and possibly other neurodegenerative diseases. (C) 2000 Academic Press.",
author = "Anne Chew and Giorgio Sirugo and Alsobrook, {John P.} and Grazia Isaya",
year = "2000",
month = "4",
day = "15",
doi = "10.1006/geno.2000.6162",
language = "English (US)",
volume = "65",
pages = "104--112",
journal = "Genomics",
issn = "0888-7543",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Functional and genomic analysis of the human mitochondrial intermediate peptidase, a putative protein partner of frataxin

AU - Chew, Anne

AU - Sirugo, Giorgio

AU - Alsobrook, John P.

AU - Isaya, Grazia

PY - 2000/4/15

Y1 - 2000/4/15

N2 - We showed recently that the yeast mitochondrial intermediate peptidase (YMIP polypeptide; gene symbol, OCT1) promotes mitochondrial iron uptake by catalyzing the maturation of iron-utilizing proteins and exacerbates the mitochondrial iron accumulation that results from loss of yeast frataxin, a mitochondrial protein required for mitochondrial iron efflux. This suggests that the human MIP (HMIP polypeptide; gene symbol MIPEP) may be one or the loci predicted to influence the clinical manifestations of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by lack of human frataxin. To begin to test this hypothesis, we have characterized HMIP at the functional and genomic levels. We show that HMIP can complement a yeast knock-out mutant lacking. YMIP, demonstrating that HMIP and YMIP are functional homologues. The MIPEP gene spans 57 kb and consists of 19 exons that correlate with the functional domains of HMIP. Primer analysis has identified major transcript of extension the MIPEP gene expressed differentially and predominantly in tissues with high oxygen consumption, while sequence analysis of ~2 kb of 5'-flanking DNA has revealed putative Mt1/3/4, NF-κB, and AP-1 elements that may regulate MIPEP expression in these tissues. Using a new polymorphic (CA), repeat in intron 4, MIPEP has been genetically mapped within a 7-cM interval between markers D13S283 and D13S217 on 13q12. This work provides the basis for molecular analysis of MIPEP in FRDA and possibly other neurodegenerative diseases. (C) 2000 Academic Press.

AB - We showed recently that the yeast mitochondrial intermediate peptidase (YMIP polypeptide; gene symbol, OCT1) promotes mitochondrial iron uptake by catalyzing the maturation of iron-utilizing proteins and exacerbates the mitochondrial iron accumulation that results from loss of yeast frataxin, a mitochondrial protein required for mitochondrial iron efflux. This suggests that the human MIP (HMIP polypeptide; gene symbol MIPEP) may be one or the loci predicted to influence the clinical manifestations of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by lack of human frataxin. To begin to test this hypothesis, we have characterized HMIP at the functional and genomic levels. We show that HMIP can complement a yeast knock-out mutant lacking. YMIP, demonstrating that HMIP and YMIP are functional homologues. The MIPEP gene spans 57 kb and consists of 19 exons that correlate with the functional domains of HMIP. Primer analysis has identified major transcript of extension the MIPEP gene expressed differentially and predominantly in tissues with high oxygen consumption, while sequence analysis of ~2 kb of 5'-flanking DNA has revealed putative Mt1/3/4, NF-κB, and AP-1 elements that may regulate MIPEP expression in these tissues. Using a new polymorphic (CA), repeat in intron 4, MIPEP has been genetically mapped within a 7-cM interval between markers D13S283 and D13S217 on 13q12. This work provides the basis for molecular analysis of MIPEP in FRDA and possibly other neurodegenerative diseases. (C) 2000 Academic Press.

UR - http://www.scopus.com/inward/record.url?scp=0034655529&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034655529&partnerID=8YFLogxK

U2 - 10.1006/geno.2000.6162

DO - 10.1006/geno.2000.6162

M3 - Article

C2 - 10783257

AN - SCOPUS:0034655529

VL - 65

SP - 104

EP - 112

JO - Genomics

JF - Genomics

SN - 0888-7543

IS - 2

ER -