Abstract 17072: Mitochondrial Import of miRNA as a Mechanism of Mitochondrial Gene Regulation
Mitochondria are semi-autonomous cellular organelles with their own genome, which not only act as the powerhouse of the cell by supplying energy through oxidative phosphorylation, but also play a destructive role through participation in cell death pathways. MicroRNAs (miRNAs) are usually 19-25 nt long, non-coding RNAs, involved in post-transcriptional gene regulation by binding to the 3'-untranslated regions (3'-UTRs) of target mRNA. Here we report a specific miRNA, miR-181c, in the mitochondrial fraction of rat heart. We find that miR-181c is encoded in the nucleus, assembled in the cytoplasm, and finally translocated into the mitochondria. Bioinformatics studies indicated that cytochrome c oxidase subunit 1 (mt-COX1) in the mitochondrial genome may be a target of miR-181c. To study whether miR-181c could regulate mt-COX1, we over-expressed precursor miR-181c (or scramble sequence) in rat neonatal ventricular cardiomyocytes (NRVM). Over-expression of miR-181c did not change mt-COX1 mRNA but significantly decreased mt-COX1 protein expression, suggesting that miR-181c acts primarily on translational regulation of mt-COX1. In addition to altering COX1, we also found that over-expression of miR-181c resulted in increased mt-COX2 mRNA and protein content. On the functional level, over-expression of miR-181c modulates mitochondrial respiration and ROS generation in NRVM. Thus, our data show for the first time that miR-181c can enter and target the mitochondrial genome, which ultimately causes electron transport chain complex IV remodeling and alters mitochondrial function. This unique observation may open a new dimension to our understanding of mitochondrial dynamics.
- © 2011 by American Heart Association, Inc.