CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation

• Published in: Nature communications Vol. 5; no. 1; p. 3596
• Main Authors: Wang, Kun, Long, Bo, Zhou, Lu-Yu, Liu, Fang, Zhou, Qun-Yong, Liu, Cui-Yun, Fan, Yuan-Yuan, Li, Pei-Feng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.04.2014; Nature Publishing Group
• Subjects: 13; 13/2; 13/95; 38; 631/337/384/2568; 631/443/592/75/2/1674; 631/80; 692/308; Animals; Apoptosis - genetics; Down-Regulation; Humanities and Social Sciences; Hypoxia - genetics; Hypoxia - metabolism; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Mitochondrial Dynamics - genetics; multidisciplinary; Myocytes, Cardiac - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4596

Abnormal mitochondrial fission participates in the pathogenesis of many diseases. Long non-coding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the regulation of mitochondrial network is unclear. Here we report that a lncRNA, named cardiac apoptosis-related lncRNA (CARL), can suppress mitochondrial fission and apoptosis by targeting miR-539 and PHB2. The results show that PHB2 is able to inhibit mitochondrial fission and apoptosis. miR-539 is responsible for the dysfunction of PHB2 and regulates mitochondrial fission and apoptosis by targeting PHB2. Further, we show that CARL can act as an endogenous miR-539 sponge that regulates PHB2 expression, mitochondrial fission and apoptosis. Our present study reveals a model of mitochondrial fission regulation that is composed of CARL, miR-539 and PHB2. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction. The prohibitin complex promotes cell survival by regulating mitochondrial morphogenesis. Wang et al. identify a long non-coding RNA that regulates this complex in cardiomyocytes by acting as a sponge to downregulate a prohibitin-targetting miRNA, protecting cells from apoptosis in anoxic conditions.