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
N1 - Funding Information:
This work was supported by a grant from the Muscular Dystrophy Association and by Grant AG15709 from the National Institute on Aging.
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.
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U2 - 10.1006/geno.2000.6162
DO - 10.1006/geno.2000.6162
M3 - Article
C2 - 10783257
AN - SCOPUS:0034655529
SN - 0888-7543
VL - 65
SP - 104
EP - 112
JO - Genomics
JF - Genomics
IS - 2
ER -