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

Alessia Indrieri, Sabrina Carrella, Alessia Romano, Alessandra Spaziano, Elena Marrocco, Erika Fernandez-Vizarra, Sara Barbato, Mariateresa Pizzo, Yulia Ezhova, Francesca M. Golia, Ludovica Ciampi, Roberta Tammaro, Jorge Henao-Mejia, Adam Williams, Richard A. Flavell, Elvira De Leonibus, Massimo Zeviani, Enrico M. Surace, Sandro Banfi*, Brunella Franco

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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.

Original languageEnglish (US)
Article numbere8734
JournalEMBO Molecular Medicine
Issue number5
StatePublished - May 2019


  • LHON
  • miR-181
  • microRNA
  • mitochondrial disease
  • neurodegeneration

ASJC Scopus subject areas

  • Molecular Medicine


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