6533b7dafe1ef96bd126ecce

RESEARCH PRODUCT

0393: Impact of miR-378* and its target desmin intermediate filament on mitochondria distribution in cardiomyocytes

subject

description

Background MiR-378 and miR-378* microRNAs are derived from an intron of the PGC-1β gene, a regulator of mitochondrial biogenesis. Their expression is either repressed or increased during heart failure depending on the model. Through proteomics approaches, we previously identified new targets of these miRs in H9c2 fetal cardiomyoblasts, among which lactate dehydrogenase for miR-378 and key cytoskeletal proteins for miR-378*. Aims To better assess its role in energy metabolism and differentiation; we overexpressed miR-378 and miR-378* in primary neonate rat cardiomyocytes (NRC) that are more differentiated and less proliferative than H9c2 cardiomyoblasts. Results We identified desmin as a new target of miR-378* in NRC. Desmin network plays a key role as a structural integrator of myofibrils and mitochondria positioning. MiR-378* overexpression reduced desmin levels and disrupted its organization. Confocal microscopy analysis of NRC stained with the mitochondrial dye MitoTracker revealed that miR-378* overexpression alters mitochondria distribution in the cell. AAV-mediated rescue of desmin expression in presence of miR-378* preserved mitochondria distribution. Mir-378 overexpression had a milder impact on cell organization than miR-378* and did not directly targetted desmin. Conclusion and perspectives These results suggest that changes in miR-378* expression level could play an important role in the coupled alteration of cytoskeletal and mitochondrial networks observed in failing myocardium. Download : Download full-size image Abstract 0393 – Figure: Biological functions regulated by miR-378/378*