miR-181a/b downregulation exerts a protective action on mitochondrial disease models.

TitlemiR-181a/b downregulation exerts a protective action on mitochondrial disease models.
Publication TypeJournal Article
Year of Publication2019
AuthorsIndrieri, A, Carrella, S, Romano, A, Spaziano, A, Marrocco, E, Fernandez-Vizarra, E, Barbato, S, Pizzo, M, Ezhova, Y, Golia, FM, Ciampi, L, Tammaro, R, Henao-Mejia, J, Williams, A, Flavell, RA, De Leonibus, E, Zeviani, M, Surace, EM, Banfi, S, Franco, B
JournalEMBO Mol Med
Date Published2019 May

Mitochondrial diseases (MDs) are a heterogeneous group of devastating and often fatal disorders due to defective oxidative phosphorylation. Despite the recent advances in mitochondrial medicine, effective therapies are still not available for these conditions. Here, we demonstrate that the microRNAs miR-181a and miR-181b (miR-181a/b) regulate key genes involved in mitochondrial biogenesis and function and that downregulation of these miRNAs enhances mitochondrial turnover in the retina through the coordinated activation of mitochondrial biogenesis and mitophagy. We thus tested the effect of miR-181a/b inactivation in different animal models of MDs, such as microphthalmia with linear skin lesions and Leber's hereditary optic neuropathy. We found that miR-181a/b downregulation strongly protects retinal neurons from cell death and significantly ameliorates the disease phenotype in all tested models. Altogether, our results demonstrate that miR-181a/b regulate mitochondrial homeostasis and that these miRNAs may be effective gene-independent therapeutic targets for MDs characterized by neuronal degeneration.

Alternate JournalEMBO Mol Med
Citation Key10.15252/emmm.201708734
PubMed ID30979712
PubMed Central IDPMC6505685