Open AccessmiR‐181a/b downregulation exerts a protective action on mitochondrial disease models
Author(s) -
Indrieri Alessia,
Carrella Sabrina,
Romano Alessia,
Spaziano Alessandra,
Marrocco Elena,
FernandezVizarra Erika,
Barbato Sara,
Pizzo Mariateresa,
Ezhova Yulia,
Golia Francesca M,
Ciampi Ludovica,
Tammaro Roberta,
HenaoMejia Jorge,
Williams Adam,
Flavell Richard A,
De Leonibus Elvira,
Zeviani Massimo,
Surace Enrico M,
Banfi Sandro,
Franco Brunella
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708734
Subject(s) - downregulation and upregulation , mitophagy , mitochondrion , mitochondrial biogenesis , biology , microbiology and biotechnology , microrna , retinal degeneration , cancer research , apoptosis , retina , autophagy , neuroscience , genetics , gene
Abstract Mitochondrial diseases ( MD s) 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 micro RNA s miR‐181a and miR‐181b (miR‐181a/b) regulate key genes involved in mitochondrial biogenesis and function and that downregulation of these mi RNA s 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 MD s, 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 mi RNA s may be effective gene‐independent therapeutic targets for MD s characterized by neuronal degeneration.