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Therapeutic potential of mitochondrial transfer in reversing mutant-to-wild-type mtDNA ratio and improving mitochondrial dysfunction in 1555A>G mtDNA mutation-associated hearing loss

Year: 2026

Type: article

Abstract: Mitochondrial DNA (mtDNA) mutations are a major cause of sensorineural hearing loss (SNHL). The m.1555A >G mutation in the mitochondrial 12S rRNA gene is closely linked to nonsyndromic and aminoglycoside-induced hearing loss, leading to impaired oxidative phosphorylation (OXPHOS) and ATP production. Current treatments focus on auditory rehabilitation without addressing mitochondrial pathology. This study investigated mitochondrial transplantation as a therapeutic approach. Fibroblasts from two patients with homoplasmic m.1555A > G mutations identified during cochlear implant surgery received allogeneic mitochondria (PN-101) derived from human umbilical cord mesenchymal stem cells. Transplantation significantly increased intracellular ATP levels, complex I activity, and OXPHOS protein expression, while protecting against kanamycin-induced mitochondrial dysfunction. Importantly, PN-101 induced a heteroplasmy shift toward wild-type mtDNA, with repeated treatments sustaining and enhancing this effect. These findings demonstrate that PN-101-mediated mitochondrial transplantation improves mitochondrial bioenergetics and modulates mtDNA heteroplasmy in m.1555A > G mutant cells, suggesting a promising disease-modifying therapy for mtDNA-related hearing loss and a potential precision medicine approach.

Source: Scientific Reports

DOI: 10.1038/s41598-026-51402-4