Document Type
Article
Publication Date
4-12-2019
Keywords
JGM
JAX Source
EMBO Mol Med 2019; 11:e8734.
ISSN
1757-4684
PMID
30979712
DOI
https://doi.org/10.15252/emmm.201708734
Abstract
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.
Recommended Citation
Indrieri A,
Carrella S,
Romano A,
Spaziano A,
Marrocco E,
Fernandez-Vizarra E,
Barbato S,
Pizzo M,
Ezhova Y,
Golia F,
Ciampi L,
Tammaro R,
Henao-Mejia J,
Williams A,
Flavell R,
De Leonibus E,
Zeviani M,
Surace E,
Banfi S,
Franco B.
miR-181a/b downregulation exerts a protective action on mitochondrial disease models. EMBO Mol Med 2019; 11:e8734.
Comments
This open access article is licensed under a Creative Commons Attribution 4.0 International License.