Document Detail

The alternative oxidase, a tool for compensating cytochrome c oxidase deficiency in human cells.
MedLine Citation:
PMID:  19493305     Owner:  NLM     Status:  MEDLINE    
In plants as well as in a number of micro-organisms, and in several animal phyla, but not in mammals, the alternative oxidase (AOX) possibly by-passes the cytochrome segment of the respiratory chain. The AOX is located at the inner surface of the inner mitochondrial membrane, being activated by over-reduction of the quinone pool and accumulation of keto-acids such as pyruvate. Since these conditions are frequently encountered in patients with mitochondrial diseases, we hypothesized that the expression of the ascidian Ciona intestinalis AOX might alleviate the consequences of a blockade of the cytochrome segment of the respiratory chain in human cells. We previously expressed the C. intestinalis AOX in human embryonic kidney (HEK 293-T-derived) cells conferring cyanide-resistance to cell respiration without any detectable detrimental effect (Hakkaart et al. 2006). We have now expressed the AOX in human cultured fibroblasts either with a functional respiratory chain (foreskin immortalized fibroblasts, BJ1-htert) or presenting a cytochrome c oxidase deficiency resulting from an impaired heme aa3 biogenesis. We used immortalized COX15-deficient skin fibroblasts from a patient who died from an early fatal cardiomyopathy. We found that the expression of the AOX in these cells was well tolerated and corrected for the various consequences of the cytochrome c oxidase deficiency in COX15-mutant cells, i.e. decreased cell respiration, glucose and pyruvate dependency. We thus validated our hypothesis that AOX could compensate for cytochrome c oxidase deficiency in human cells.
Emmanuel P Dassa; Eric Dufour; Sergio Goncalves; Howard T Jacobs; Pierre Rustin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-25
Journal Detail:
Title:  Physiologia plantarum     Volume:  137     ISSN:  1399-3054     ISO Abbreviation:  Physiol Plant     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-27     Completed Date:  2010-01-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1256322     Medline TA:  Physiol Plant     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  427-34     Citation Subset:  IM    
Inserm, U676 and Universit?? Paris 7, Facult?? de M??decine Denis Diderot, Paris, France.
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MeSH Terms
Cell Line, Transformed
Cell Proliferation / drug effects
Cell Respiration / drug effects
Ciona intestinalis / enzymology
Culture Media
Cyanides / toxicity
Electron Transport Complex IV / metabolism*
Fibroblasts / drug effects,  enzymology*,  pathology
Mitochondria / drug effects,  enzymology
Oxidation-Reduction / drug effects
Oxidoreductases / metabolism*
Substrate Specificity / drug effects
Reg. No./Substance:
0/Culture Media; 0/Cyanides; EC 1.-/Oxidoreductases; EC 1.-/alternative oxidase; EC Transport Complex IV

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