MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADD.

Rationale: Necrosis is one of the main forms of cardiomyocyte death in heart disease. Recent studies have demonstrated that certain types of necrosis are regulated and programmed dependent on the activation of receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3 which may be negatively regulated by Fas-associated protein with death domain (FADD). In addition, microRNAs and long noncoding RNAs have been shown to play important roles in various biological processes recently.

Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w.

MicroRNAs (miRNAs) are small non-coding RNAs, and they bind to complementary sequences in the three prime untranslated regions (3' UTRs) of target mRNA transcripts, thereby inhibiting mRNA translation or promoting mRNA degradation. Excessive reactive oxygen species (ROS) can cause cell-damaging effects through oxidative modification of macromolecules leading to their inappropriate functions. Such oxidative modification is related to cancers, aging, and neurodegenerative and cardiovascular diseases.

A pre-microRNA-149 (miR-149) genetic variation affects miR-149 maturation and its ability to regulate the Puma protein in apoptosis.

MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs that function as negative regulators of gene expression. They are transcribed from endogenous DNA and form hairpin structures (termed as pre-miRNAs) that are processed to form mature miRNAs. It remains largely unknown as to the molecular consequences of the natural genetic variation in pre-miRNAs.

Mitochondrial function in cardiac hypertrophy.

Cardiac hypertrophic program is a chronic, complex process, and occurs in response to long-term increases of hemodynamic load related to a variety of pathophysiological conditions. Mitochondria, known as "the cellular power plants", occupy about one-third of cardiomyocyte volume and supply roughly 90% of the adenosine triphosphate (ATP). Impairment of energy metabolism has been regarded as one of the main pathogenesis of cardiac hypertrophy.

Mitochondrial network in the heart.

Mitochondria are subcellular organelles that provide energy for the cell. They form a dynamic tubular network and play an important role in maintaining the cell function and integrity. Heart is a powerful organ that supplies the motivation for circulation, thereby requiring large amounts of energy.

miR-484 regulates mitochondrial network through targeting Fis1.

Mitochondria constantly undergo fusion and fission, two necessary processes for the maintenance of organelle fidelity. The abnormal mitochondrial fission participates in the pathogenesis of many diseases, but its regulation remains poorly understood. Here we show that miR-484 can suppress translation of mitochondrial fission protein Fis1, and inhibit Fis1-mediated fission and apoptosis in cardiomyocytes and in the adrenocortical cancer cells.

miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1.

Myocardial infarction is a leading cause of mortality worldwide. Here we report that modulation of microRNA-499 (miR-499) levels affects apoptosis and the severity of myocardial infarction and cardiac dysfunction induced by ischemia-reperfusion. We found that both the α- and β-isoforms of the calcineurin catalytic subunit are direct targets of miR-499 and that miR-499 inhibits cardiomyocyte apoptosis through its suppression of calcineurin-mediated dephosphorylation of dynamin-related protein-1 (Drp1), thereby decreasing Drp1 accumulation in mitochondria and Drp1-mediated activation of the mitochondrial fission program.