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Necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. MicroRNAs (miRNAs) have emerged as key gene regulators in many diseases. However, how miRNAs contribute to programmed necrosis is poorly defined. Here we report that miR-2861 and adenine nucleotide translocase 1 (ANT1) constitute an axis that regulates necrotic cell death in the heart. Our results show that ANT1 inhibits H 2 O 2 -induced cardiomyocytes necrosis. ANT1 also antagonizes myocardial necrosis in a mouse ischemia/reperfusion (I/R) model. We further demonstrate that miR-2861 directly binds to the coding sequence of ANT1 and suppresses the expression of ANT1 mRNA and protein. MiR-2861 induces necrotic cell death. In contrast, knockdown of miR-2861 attenuates H 2 O 2 -induced necrosis in cardiomyocytes. Also, miR-2861 knockdown protects heart from I/R injury and necrotic cell death in vivo. MiR-2861 regulates necrosis and myocardial infarction through targeting ANT1. Collectively, these data identify miR-2861 and ANT1 as two novel regulators of cardiomyocyte necrosis and myocardial infarction, and suggest potential therapeutic targets in treatment of cardiac diseases. [ABSTRACT FROM AUTHOR]

Abstract: 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. Thus, we summarize here the molecular events of mitochondrial adaptations, including the mitochondrial genesis, ATP generation, ROS signaling and Ca2+ homeostasis in cardiac hypertrophy, expecting that this effort will shed new light on understanding the maladaptive cardiac remodeling. [Copyright &y& Elsevier]