biostudies-literatureCapristo MMinistero della SaluteTelethon90https://www.ebi.ac.uk/biostudies/studies/S-EPMC9347137biostudies-literatureUnknown28(1)<h4>Background</h4>Myoclonus, Epilepsy and Ragged-Red-Fibers (MERRF) is a mitochondrial encephalomyopathy due to heteroplasmic mutations in mitochondrial DNA (mtDNA) most frequently affecting the tRNA^Lys gene at position m.8344A > G. Defective tRNA^Lys severely impairs mitochondrial protein synthesis and respiratory chain when a high percentage of mutant heteroplasmy crosses the threshold for full-blown clinical phenotype. Therapy is currently limited to symptomatic management of myoclonic epilepsy, and supportive measures to counteract muscle weakness with co-factors/supplements.<h4>Methods</h4>We tested two therapeutic strategies to rescue mitochondrial function in cybrids and fibroblasts carrying different loads of the m.8344A > G mutation. The first strategy was aiMolecular medicine (Cambridge, Mass.)Rapamycin rescues mitochondrial dysfunction in cells carrying the m.8344A > G mutation in the mitochondrial tRNA^Lys.PMC9347137GGP20115Carelli VMaresca AMontopoli MCaporali LLa Morgia CFiorini CCapristo MTropeano CVDel Dotto VValentino MLfalseRapamycin rescues mitochondrial dysfunction in cells carrying the m.8344A > G mutation in the mitochondrial tRNA^Lys.<h4>Background</h4>Myoclonus, Epilepsy and Ragged-Red-Fibers (MERRF) is a mitochondrial encephalomyopathy due to heteroplasmic mutations in mitochondrial DNA (mtDNA) most frequently affecting the tRNA^Lys gene at position m.8344A > G. Defective tRNA^Lys severely impairs mitochondrial protein synthesis and respiratory chain when a high percentage of mutant heteroplasmy crosses the threshold for full-blown clinical phenotype. Therapy is currently limited to symptomatic management of myoclonic epilepsy, and supportive measures to counteract muscle weakness with co-factors/supplements.<h4>Methods</h4>We tested two therapeutic strategies to rescue mitochondrial function in cybrids and fibroblasts carrying different loads of the m.8344A > G mutation. The first strategy was ai2022-01-01T00:00:00Z2022 Aug2025-04-26T11:57:03.765Z2025-02-18T22:39:49.99ZS-EPMC93471373592276610.1186/s10020-022-00519-z