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Mitochondrial Uncoupler Carbonyl Cyanide m-Chlorophenylhydrazone Induces the Multimer Assembly and Activity of Repair Enzyme Protein L-Isoaspartyl Methyltransferase.
MedLine Citation:
PMID:  23319267     Owner:  NLM     Status:  Publisher    
The protein L-isoaspartyl methyltransferase (PIMT) repairs damaged aspartyl residues in proteins. It is commonly described as a cytosolic protein highly expressed in brain tissues. Here, we report that PIMT is an active monomeric as well as a multimeric protein in mitochondria isolated from neuroblastoma cells. Upon treatments with mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), PIMT monomers level decreased by half while that of PIMT multimers was higher. Gel electrophoresis under reducing conditions of CCCP-induced PIMT multimers led to PIMT monomers accumulation, indicating that multimers resulted from disulfide-linked PIMT monomers. The antioxidant ascorbic acid significantly lowered CCCP-induced formation of PIMT multimers, suggesting that reactive oxygen species contributed to PIMT multimerization. In addition, the elevation of PIMT multimers catalytic activity upon treatments with CCCP was severely inhibited by the reducing agent dithiothreitol. This indicated that PIMT monomers have lower enzymatic activity following CCCP treatments and that activation of PIMT multimers is essentially dependent on the formation of disulfide-linked monomers of PIMT. Furthermore, the perturbation of mitochondrial function by CCCP promoted the accumulation of damaged aspartyl residues in proteins with high molecular weights. Thus, this study demonstrates the formation of active PIMT multimers associated with mitochondria that could play a key role in repairing damaged proteins accumulating during mitochondrial dysfunction.
Irvens Fanélus; Richard R Desrosiers
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-15
Journal Detail:
Title:  Journal of molecular neuroscience : MN     Volume:  -     ISSN:  1559-1166     ISO Abbreviation:  J. Mol. Neurosci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002991     Medline TA:  J Mol Neurosci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
The Montreal General Hospital, McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
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