Document Detail


Impairment of mitochondrial tRNAIle processing by a novel mutation associated with chronic progressive external ophthalmoplegia.
MedLine Citation:
PMID:  21292040     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We report a sporadic case of chronic progressive external ophthalmoplegia associated with ragged red fibers. The patient presented with enlarged mitochondria with deranged internal architecture and crystalline inclusions. Biochemical studies showed reduced activities of complex I, III and IV in skeletal muscle. Molecular genetic analysis of all mitochondrial tRNAs revealed a G to A transition at nt 4308; the G is a highly conserved nucleotide that participates in a GC base-pair in the T-stem of mammalian mitochondrial tRNA(Ile). The mutation was detected at a high level (approx. 50%) in muscle but not in blood. The mutation co-segregated with the phenotype, as the mutation was absent from blood and muscle in the patient's healthy mother. Functional characterization of the mutation revealed a six-fold reduced rate of tRNA(Ile) precursor 3' end maturation in vitro by tRNAse Z. Furthermore, the mutated tRNA(Ile) displays local structural differences from wild-type. These results suggest that structural perturbations reduce efficiency of tRNA(Ile) precursor 3' end processing and contribute to the molecular pathomechanism of this mutation.
Authors:
A Schaller; R Desetty; D Hahn; C B Jackson; J-M Nuoffer; S Gallati; L Levinger
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-01
Journal Detail:
Title:  Mitochondrion     Volume:  11     ISSN:  1872-8278     ISO Abbreviation:  Mitochondrion     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-12     Completed Date:  2011-07-25     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  100968751     Medline TA:  Mitochondrion     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  488-96     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 © Elsevier B.V. and Mitochondria Research Society. All rights reserved. Published by Elsevier B.V. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Electron Transport Complex I / metabolism
Electron Transport Complex III / metabolism
Electron Transport Complex IV / metabolism
Female
Humans
Mitochondrial Diseases / genetics,  pathology*
Muscle, Skeletal / enzymology,  physiopathology
Ophthalmoplegia, Chronic Progressive External / genetics,  pathology*
Point Mutation*
RNA / genetics,  metabolism
RNA Processing, Post-Transcriptional*
RNA, Transfer, Ile / genetics*,  metabolism*
Grant Support
ID/Acronym/Agency:
R15 CA120072/CA/NCI NIH HHS; R15 CA120072-01/CA/NCI NIH HHS; R15CA12072/CA/NCI NIH HHS; SC3 GM084764/GM/NIGMS NIH HHS; SC3 GM084764-01/GM/NIGMS NIH HHS; SC3GM08153/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Transfer, Ile; 0/RNA, mitochondrial; 63231-63-0/RNA; EC 1.10.2.2/Electron Transport Complex III; EC 1.6.5.3/Electron Transport Complex I; EC 1.9.3.1/Electron Transport Complex IV
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Mitochondrial DNA variations associated with recurrent pregnancy loss among Indian women.
Next Document:  Revisiting the Cholinergic Hypothesis of Behavioral and Psychological Symptoms in Dementia of the Al...