| The alternative oxidase, a tool for compensating cytochrome c oxidase deficiency in human cells. | |
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MedLine Citation:
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PMID: 19493305 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Emmanuel P Dassa; Eric Dufour; Sergio Goncalves; Howard T Jacobs; Pierre Rustin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-25 |
Journal Detail:
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Title: Physiologia plantarum Volume: 137 ISSN: 1399-3054 ISO Abbreviation: Physiol Plant Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-27 Completed Date: 2010-01-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1256322 Medline TA: Physiol Plant Country: Denmark |
Other Details:
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Languages: eng Pagination: 427-34 Citation Subset: IM |
Affiliation:
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Inserm, U676 and Universit?? Paris 7, Facult?? de M??decine Denis Diderot, Paris, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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 Foreskin Humans Male Mitochondria / drug effects, enzymology Oxidation-Reduction / drug effects Oxidoreductases / metabolism* Substrate Specificity / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Culture Media; 0/Cyanides; EC 1.-/Oxidoreductases; EC 1.-/alternative oxidase; EC 1.9.3.1/Electron Transport Complex IV |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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