Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment

Abstract Mitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we...

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Autores principales:	Hideki Maeda, Daisuke Kami, Ryotaro Maeda, Akira Shikuma, Satoshi Gojo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/382aa1c322d84db991fd3411ff052609
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spelling	oai:doaj.org-article:382aa1c322d84db991fd3411ff0526092021-12-02T16:53:19ZGeneration of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment10.1038/s41598-021-90316-12045-2322https://doaj.org/article/382aa1c322d84db991fd3411ff0526092021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90316-1https://doaj.org/toc/2045-2322Abstract Mitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we present a procedure to generate mitochondrial DNA-replaced somatic cells with a combination of a temporal reduction in endogenous mitochondrial DNA and coincubation with exogeneous isolated mitochondria. Heteroplasmy in mitochondrial disease patient-derived fibroblasts in which the mutant genotype was dominant over the wild-type genotype was reversed. Mitochondrial disease patient-derived fibroblasts regained respiratory function and showed lifespan extension. Mitochondrial membranous components were utilized as a vehicle to deliver the genetic materials into endogenous mitochondria-like horizontal genetic transfer in prokaryotes. Mitochondrial DNA-replaced cells could be a resource for transplantation to treat maternal inherited mitochondrial diseases.Hideki MaedaDaisuke KamiRyotaro MaedaAkira ShikumaSatoshi GojoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hideki Maeda Daisuke Kami Ryotaro Maeda Akira Shikuma Satoshi Gojo Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment
description	Abstract Mitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we present a procedure to generate mitochondrial DNA-replaced somatic cells with a combination of a temporal reduction in endogenous mitochondrial DNA and coincubation with exogeneous isolated mitochondria. Heteroplasmy in mitochondrial disease patient-derived fibroblasts in which the mutant genotype was dominant over the wild-type genotype was reversed. Mitochondrial disease patient-derived fibroblasts regained respiratory function and showed lifespan extension. Mitochondrial membranous components were utilized as a vehicle to deliver the genetic materials into endogenous mitochondria-like horizontal genetic transfer in prokaryotes. Mitochondrial DNA-replaced cells could be a resource for transplantation to treat maternal inherited mitochondrial diseases.
format	article
author	Hideki Maeda Daisuke Kami Ryotaro Maeda Akira Shikuma Satoshi Gojo
author_facet	Hideki Maeda Daisuke Kami Ryotaro Maeda Akira Shikuma Satoshi Gojo
author_sort	Hideki Maeda
title	Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment
title_short	Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment
title_full	Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment
title_fullStr	Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment
title_full_unstemmed	Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment
title_sort	generation of somatic mitochondrial dna-replaced cells for mitochondrial dysfunction treatment
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/382aa1c322d84db991fd3411ff052609
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Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment

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