Mitochondrial MiRNA in Cardiovascular Function and Disease

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs functioning as crucial post-transcriptional regulators of gene expression involved in cardiovascular development and health. Recently, mitochondrial miRNAs (mitomiRs) have been shown to modulate the translational activity of the mitochondrial genome and regulating mitochondrial protein expression and function. Although mitochondria have been verified to be essential for the development and as a therapeutic target for cardiovascular diseases, we are just beginning to understand the roles of mitomiRs in the regulation of crucial biological processes, including energy metabolism, oxidative stress, inflammation, and apoptosis. In this review, we summarize recent findings regarding how mitomiRs impact on mitochondrial gene expression and mitochondrial function, which may help us better understand the contribution of mitomiRs to both the regulation of cardiovascular function under physiological conditions and the pathogenesis of cardiovascular diseases.

Keywords: cardiovascular disease; miRNA; mitochondria; mitomiR.

Figure 1

Illustration of mitomiR origin and functioning site in the cell. Some mature miRNAs are imported into mitochondria after the pre-miRNA originated from the nucleus are processed by DICER. The other mitomiRs may be originated from mitochondrial genome-derived mRNA molecules. All mitomiRs can exert post-transcriptional modification in the mitochondria. Imported miRNAs may also target and function at nuclear-encoded mRNAs localized on the mitochondrial surface. However, the mechanisms underlying mitomiRs biogenesis and action site are still poorly understood.

Figure 2

MitomiRs activity in vascular diseases: anti- or pro-angiogenic role. Some mitomiRs, such as miR-181a, miR-34a, and miR-146a, inhibit angiogenesis through suppressing antioxidant and anti-apoptotic mitochondrial protein to increase ROS production and cell apoptosis. Meanwhile, others, such as miR-21 and miR-210, play a pro-angiogenic role through enhancing mitochondria-mediated apoptosis pathways.