A microRNA's journey to the center of the mitochondria

MicroRNAs (miRNAs) are known as the master regulators of gene expression, and for the last two decades our knowledge of their functional reach keeps expanding. Recent studies have shown that a miRNA's role in regulation extends to extracellular and intracellular organelles. Several studies have shown a role for miRNA in regulating the mitochondrial genome in normal and disease conditions. Mitochondrial dysfunction occurs in many human pathologies, such as cardiovascular disease, diabetes, cancer, and neurological diseases. These studies have shed some light on regulation of the mitochondrial genome as well as helped to explain the role of miRNA in altering mitochondrial function and the ensuing effects on cells. Although the field has grown in recent years, many questions still remain. For example, little is known about how nuclear-encoded miRNAs translocate to the mitochondrial matrix. Knowledge of the mechanisms of miRNA transport into the mitochondrial matrix is likely to provide important insights into our understanding of disease pathophysiology and could represent new targets for therapeutic intervention. For this review, our focus will be on the role of a subset of miRNAs, known as MitomiR, in mitochondrial function. We also discuss the potential mechanisms used by these nuclear-encoded miRNAs for import into the mitochondrial compartment.