{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:22:16Z","timestamp":1791246136138,"version":"4.1.0"},"reference-count":0,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:00:00Z","timestamp":1180656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rejuvenation Research"],"published-print":{"date-parts":[[2007,6]]},"abstract":"\n The possibility of synthesizing mitochondrial DNA (mtDNA)-coded proteins in the cytosolic compartment, called allotopic expression, provides an attractive option for genetic treatment of human diseases caused by mutations of the corresponding genes. However, it is now appreciated that the high hydrophobicity of proteins encoded by the mitochondrial genome represents a strong limitation on their mitochondrial import when translated in the cytosol. Recently, we optimized the allotopic expression of a recoded\n ATP6<\/jats:italic>\n gene in human cells, by forcing its mRNA to localize to the mitochondrial surface. In this study, we show that this approach leads to a long-lasting and complete rescue of mitochondrial dysfunction of fibroblasts harboring the neurogenic muscle weakness, ataxia and retinitis Pigmentosa T8993G\n ATP6<\/jats:italic>\n mutation or the Leber hereditary optic neuropathy G11778A\n ND4<\/jats:italic>\n mutation. The recoded\n ATP6<\/jats:italic>\n gene was associated with the\n cis<\/jats:italic>\n -acting elements of\n SOD2<\/jats:italic>\n , while the\n ND4<\/jats:italic>\n gene was associated with the\n cis<\/jats:italic>\n -acting elements of\n COX10<\/jats:italic>\n . Both\n ATP6<\/jats:italic>\n and\n ND4<\/jats:italic>\n gene products were efficiently translocated into the mitochondria and functional within their respective respiratory chain complexes. Indeed, the abilities to grow in galactose and to produce adenosine triphosphate (ATP)\n in vitro<\/jats:italic>\n were both completely restored in fibroblasts allotopically expressing either\n ATP6<\/jats:italic>\n or\n ND4<\/jats:italic>\n . Notably, in fibroblasts harboring the\n ATP6<\/jats:italic>\n mutation, allotopic expression of\n ATP6<\/jats:italic>\n led to the recovery of complex V enzymatic activity. Therefore, mRNA sorting to the mitochondrial surface represents a powerful strategy that could ultimately be applied in human therapy and become available for an array of devastating disorders caused by mtDNA mutations.\n <\/jats:p>","DOI":"10.1089\/rej.2006.0526","type":"journal-article","created":{"date-parts":[[2007,5,23]],"date-time":"2007-05-23T11:17:50Z","timestamp":1179919070000},"page":"127-144","source":"Crossref","is-referenced-by-count":88,"title":["Allotopic mRNA Localization to the Mitochondrial Surface Rescues Respiratory Chain Defects in Fibroblasts Harboring Mitochondrial DNA Mutations Affecting Complex I or V Subunits"],"prefix":"10.1177","volume":"10","author":[{"given":"Crystel","family":"Bonnet","sequence":"first","affiliation":[{"name":"Laboratoire de Physiopathologie Cellulaire et Mol\u00e9culaire de la R\u00e9tine, INSERM U592, Universit\u00e9 Pierre et Marie Curie (UPMC-Paris6), H\u00f4pital St. Antoine\u2013B\u00e2t. Kourilsky, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Kaltimbacher","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie Cellulaire et Mol\u00e9culaire de la R\u00e9tine, INSERM U592, Universit\u00e9 Pierre et Marie Curie (UPMC-Paris6), H\u00f4pital St. Antoine\u2013B\u00e2t. Kourilsky, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Ellouze","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie Cellulaire et Mol\u00e9culaire de la R\u00e9tine, INSERM U592, Universit\u00e9 Pierre et Marie Curie (UPMC-Paris6), H\u00f4pital St. Antoine\u2013B\u00e2t. Kourilsky, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Augustin","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie Cellulaire et Mol\u00e9culaire de la R\u00e9tine, INSERM U592, Universit\u00e9 Pierre et Marie Curie (UPMC-Paris6), H\u00f4pital St. Antoine\u2013B\u00e2t. Kourilsky, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paule","family":"B\u00e9nit","sequence":"additional","affiliation":[{"name":"INSERM U676, H\u00f4pital Robert Debr\u00e9 48, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Forster","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie Cellulaire et Mol\u00e9culaire de la R\u00e9tine, INSERM U592, Universit\u00e9 Pierre et Marie Curie (UPMC-Paris6), H\u00f4pital St. Antoine\u2013B\u00e2t. Kourilsky, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Rustin","sequence":"additional","affiliation":[{"name":"INSERM U676, H\u00f4pital Robert Debr\u00e9 48, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9-Alain","family":"Sahel","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie Cellulaire et Mol\u00e9culaire de la R\u00e9tine, INSERM U592, Universit\u00e9 Pierre et Marie Curie (UPMC-Paris6), H\u00f4pital St. Antoine\u2013B\u00e2t. Kourilsky, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Corral-Debrinski","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie Cellulaire et Mol\u00e9culaire de la R\u00e9tine, INSERM U592, Universit\u00e9 Pierre et Marie Curie (UPMC-Paris6), H\u00f4pital St. Antoine\u2013B\u00e2t. Kourilsky, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2007,6]]},"container-title":["Rejuvenation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/rej.2006.0526","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/rej.2006.0526","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T01:28:00Z","timestamp":1777685280000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.1089\/rej.2006.0526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,6]]}},"alternative-id":["10.1089\/rej.2006.0526"],"URL":"https:\/\/doi.org\/10.1089\/rej.2006.0526","relation":{},"ISSN":["1549-1684","1557-8577"],"issn-type":[{"value":"1549-1684","type":"print"},{"value":"1557-8577","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6]]}}}