title: Mitofusin 1 is negatively regulated by microRNA 140 in cardiomyocyte apoptosis.
abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs that mediate posttranscriptional gene silencing. Mitochondrial fission participates in the induction of apoptosis. It remains largely unknown whether miRNAs can regulate mitochondrial fission. Reactive oxygen species and doxorubicin could induce mitochondrial fission and apoptosis in cardiomyocytes. Concomitantly, mitofusin 1 (Mfn1) was downregulated, whereas miRNA 140 (miR-140) was upregulated upon apoptotic stimulation. We investigated whether Mfn1 and miR-140 play a functional role in mitochondrial fission and apoptosis. Ectopic expression of Mfn1 attenuated mitochondrial fission and apoptosis. Knockdown of miR-140 inhibited mitochondrial fission. Our results further revealed that knockdown of miR-140 was able to reduce myocardial infarct sizes in an animal model. We observed that miR-140 could suppress the expression of Mfn1, and it exerted its effect on mitochondrial fission and apoptosis through targeting Mfn1. Our data revealed that mitochondrial fission occurs in cardiomyocytes and can be counteracted by Mfn1. However, the function of Mfn1 is negatively regulated by miR-140. Our present work suggests that Mfn1 and miR-140 are integrated into the program of cardiomyocyte apoptosis.
authors.affiliation: Department of Physiology, Shantou University School of Medicine, Shantou, China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Li
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Li
authors.forename: Jianqin
authors.initials: J
authors.lastname: Jiao
authors.forename: Jianxun
authors.initials: J
authors.lastname: Wang
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Li
authors.forename: Danian
authors.initials: D
authors.lastname: Qin
authors.forename: Peifeng
authors.initials: P
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004706:Endodeoxyribonucleases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008929:Mitochondria, Heart / Q000502:physiology; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology*; D034622:RNA Interference; D051381:Rats
chemical_list: D020413:3' Untranslated Regions; C580706:MIRN140 microRNA, rat; D008565:Membrane Proteins; C489709:Mfn1 protein, rat; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D004706:Endodeoxyribonucleases; C052391:endonuclease G