Mitochondrial noncoding RNA-regulatory network in cardiovascular disease.

ABSTRACT

Mitochondrial function and integrity are vital for the maintenance of cellular homeostasis, particularly in high-energy demanding cells. Cardiomyocytes have a large number of mitochondria, which provide a continuous and bulk supply of the ATP necessary for cardiac mechanical function. More than 90% of the ATP consumed by the heart is derived from the mitochondrial oxidative metabolism. Decreased energy supply as the main consequence of mitochondrial dysfunction is closely linked to cardiovascular disease (CVD). The discovery of noncoding RNA (ncRNAs) in the mitochondrial compartment has changed the traditional view of molecular pathways involved in the regulatory network of CVD. Mitochondrial ncRNAs participate in controlling cardiovascular pathogenesis by regulating glycolysis, mitochondrial energy status, and the expression of genes involved in mitochondrial metabolism. Understanding the underlying mechanisms of the association between impaired mitochondrial function resulting from fluctuation in expression levels of ncRNAs and specific disease phenotype can aid in preventing and treating CVD. This review presents an overview of the role of mitochondrial ncRNAs in the complex regulatory network of the cardiovascular pathology. We will summarize and discuss (1) mitochondrial microRNAs (mitomiRs) and long noncoding RNAs (lncRNAs) encoded either by nuclear or mitochondrial genome which are involved in the regulation of mitochondrial metabolism; (2) the role of mitomiRs and lncRNAs in the pathogenesis of several CVD such as hypertension, cardiac hypertrophy, acute myocardial infarction and heart failure; (3) the biomarker and therapeutic potential of mitochondrial ncRNAs in CVD; (4) and the challenges inherent to their translation into clinical application.