Recovery of MERRF fibroblasts and cybrids pathophysiology by coenzyme Q10.

Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics
Mario De la MataJosé A Sánchez-Alcázar

Abstract

Mitochondrial DNA mutations are an important cause of human disease for which there is no effective treatment. Myoclonic epilepsy with ragged-red fibers (MERRF) is a mitochondrial disease usually caused by point mutations in transfer RNA genes encoded by mitochondrial DNA. The most common mutation associated with MERRF syndrome, m.8344A > G in the gene MT-TK, which encodes transfer RNA(Lysine), affects the translation of all mitochondrial DNA encoded proteins. This impairs the assembly of the electron transport chain complexes leading to decreased mitochondrial respiratory function. Here we report on how this mutation affects mitochondrial function in primary fibroblast cultures established from patients harboring the A8344G mutation. Coenzyme Q10 levels, as well as mitochondrial respiratory chain activity, and mitochondrial protein expression levels were significantly decreased in MERRF fibroblasts. Mitotracker staining and imaging analysis of individual mitochondria indicated the presence of small, rounded, depolarized mitochondria in MERRF fibroblasts. Mitochondrial dysfunction was associated with increased oxidative stress and increased degradation of impaired mitochondria by mitophagy. Transmitochondrial cybrids harboring ...Continue Reading

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Citations

Nov 3, 2015·Expert Opinion on Therapeutic Targets·Marina Villanueva PazJosé A Sánchez-Alcázar
Jun 16, 2015·Free Radical Biology & Medicine·Genki Hayashi, Gino Cortopassi
May 31, 2015·Journal of Inherited Metabolic Disease·Rikke K J OlsenNiels Gregersen
Apr 8, 2014·Biochimica Et Biophysica Acta·María MoránMiguel A Martín
May 21, 2014·The International Journal of Biochemistry & Cell Biology·Chin-San LiuSheng-Fei Chuang
Jan 13, 2015·Experimental and Therapeutic Medicine·Xue-Fan YuHong-Mei Meng
May 8, 2019·Expert Opinion on Pharmacotherapy·Josef Finsterer
May 16, 2019·Journal of Zhejiang University. Science. B·Shuang-Yi HuQing-Feng Yan
Jun 24, 2018·International Journal of Molecular Sciences·Alessia FabbriCarla Fiorentini
Feb 11, 2020·Frontiers in Physiology·Peter M MasschelinSean M Hartig
Sep 22, 2017·Diseases·Juan M Suárez-RiveroJosé A Sánchez-Alcázar
Jul 22, 2018·Essays in Biochemistry·Valerio Carelli, Chiara La Morgia
May 6, 2020·International Journal of Molecular Sciences·Teresa Galera-MongeM Esther Gallardo
Jan 9, 2020·Clinical Genetics·Ester López-GallardoEduardo Ruiz-Pesini
Jan 30, 2021·Frontiers in Genetics·Suleva Povea-CabelloJosé A Sánchez-Alcázar
Mar 17, 2021·Investigative Ophthalmology & Visual Science·Jessica M SkeieMark A Greiner
Feb 18, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Marina Villanueva-PazJosé A Sánchez-Alcázar

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