PT  - JOURNAL ARTICLE
AU  - Ai Vu Hong
AU  - Nathalie Bourg
AU  - Peggy Sanatine
AU  - Jerome Poupiot
AU  - Karine Charton
AU  - Evelyne Gicquel
AU  - Emmanuelle Massourides
AU  - Marco Spinazzi
AU  - Isabelle Richard
AU  - David Israeli
TI  - Dlk1-Dio3 cluster miRNAs regulate mitochondrial functions in the dystrophic muscle in Duchenne muscular dystrophy
AID  - 10.26508/lsa.202201506
DP  - 2023 Jan 01
TA  - Life Science Alliance
PG  - e202201506
VI  - 6
IP  - 1
4099  - https://www.life-science-alliance.org/content/6/1/e202201506.short
4100  - https://www.life-science-alliance.org/content/6/1/e202201506.full
SO  - Life Sci. Alliance2023 Jan 01; 6
AB  - Duchenne muscular dystrophy (DMD) is a severe muscle disease caused by impaired expression of dystrophin. Whereas mitochondrial dysfunction is thought to play an important role in DMD, the mechanism of this dysfunction remains to be clarified. Here we demonstrate that in DMD and other muscular dystrophies, a large number of Dlk1-Dio3 clustered miRNAs (DD-miRNAs) are coordinately up-regulated in regenerating myofibers and in the serum. To characterize the biological effect of this dysregulation, 14 DD-miRNAs were simultaneously overexpressed in vivo in mouse muscle. Transcriptomic analysis revealed highly similar changes between the muscle ectopically overexpressing 14 DD-miRNAs and the mdx diaphragm, with naturally up-regulated DD-miRNAs. Among the commonly dysregulated pathway we found repressed mitochondrial metabolism, and oxidative phosphorylation (OxPhos) in particular. Knocking down the DD-miRNAs in iPS-derived skeletal myotubes resulted in increased OxPhos activities. The data suggest that (1) DD-miRNAs are important mediators of dystrophic changes in DMD muscle, (2) mitochondrial metabolism and OxPhos in particular are targeted in DMD by coordinately up-regulated DD-miRNAs. These findings provide insight into the mechanism of mitochondrial dysfunction in muscular dystrophy.