miR-181a/b downregulation exerts a protective action on mitochondrial disease models.
Golia, Francesca M
Flavell, Richard A
De Leonibus, Elvira
Surace, Enrico M
EMBO Molecular Medicine
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Indrieri, A., Carrella, S., Romano, A., Spaziano, A., Marrocco, E., Fernandez-Vizarra, E., Barbato, S., et al. (2019). miR-181a/b downregulation exerts a protective action on mitochondrial disease models.. EMBO Molecular Medicine, 11 (e8734)https://doi.org/10.15252/emmm.201708734
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.
LHON, miR‐181, microRNA, mitochondrial disease, neurodegeneration
Italian Fondazione Telethon (grant no. TGM16YGM02 to S. Ban, the Fondazione Roma (grant no. RP‐201300000009 to S. Ban)) and the AFM‐Telethon (grant no. 20685 to B.F.). A.I. received an Umberto Veronesi Fellowship. This research was carried out in the frame of Programme STAR, financially supported by UniNA and Compagnia di San Paolo (Bando STAR, 16‐CSP‐UNINA‐048, to A.I).
External DOI: https://doi.org/10.15252/emmm.201708734
This record's URL: https://www.repository.cam.ac.uk/handle/1810/296826
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/