Interplay of Mitochondrial miRNA (mito-miRNAs) in Mitochondrial Disorders

Mitochondria are important organelles in cellular metabolism. Several crucial metabolic pathways such as the energy-producing electron transport chain or the tricarboxylic acid cycle are hosted inside the mitochondria. The proper function of mitochondria depends on the import of proteins, which are encoded in the nucleus and synthesized in the cytosol. Micro-ribonucleic acids (miRNAs) are short non-coding ribonucleic acid (RNA) molecules with the ability to prevent messenger RNA (mRNA)-translation or to induce the degradation of mRNA-transcripts. Although miRNAs are mainly located in the cytosol or the nucleus, a subset of ~150 different miRNAs, called mitomiRs, has also been found localized to mitochondrial fractions of cells and tissues together with the subunits of the RNA-induced silencing complex (RISC); the protein complex through which miRNAs normally act to prevent translation of their mRNA-targets. A number of functions of mitomiRs are possible. Since cytosolic miRNAs inhibit protein translation, a likely function of mitomiRs is to suppress the mRNA translation of mitochondrial proteins, thus regulating the mitochondrial proteome.

Mitochondrial diseases are chronic (long-term), genetic, often inherited disorders that occur when mitochondria fail to produce enough energy for the body to function properly. Healthy mitochondria are prerequisites for a cell to survive and its dysfunction is seen in several human pathologies that include cardiovascular disease, obesity, diabetes, neurodegeneration, and cancer. Hence, mitochondria represent an attractive target to treat complex human pathophysiologies. The available pieces of evidence suggest a new framework for considering and understanding mitomiR as a novel biomarker in the mitochondrial dysfunctions linking it with many complex diseases. It has been established that mitomiRs can regulate gene expression, suggesting that after translocation, mitomiRs can bind to the 3¢-end of a mitochondrial gene. A lot needs to be understood regarding the import of miRNAs into mitochondrial sub-compartments and miRNA regulatory networks within the organelle. There is no concrete evidence that suggests that the mitochondrial genome can also encode miRNA(s). Although the sequence of miR-1974, miR-1977, and miR-1978 have been observed in mitochondrial DNA much needs to be explored before they can enter clinics. The detailed and better understanding of the biogenesis, import, and function of mitomiR is still in its infancy but might provide a novel strategy to deal with complex mitochondrial-associated human diseases.

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