Irisin activates Opa1-induced mitophagy to protect cardiomyocytes against apoptosis following myocardial infarction.

Aging
Ting Xin, Chengzhi Lu

Abstract

Myocardial infarction is characterized by sudden ischemia and cardiomyocyte death. Mitochondria have critical roles in regulating cardiomyocyte viability and can sustain damage under ischemic conditions. Mitophagy is a mechanism by which damaged mitochondria are removed by autophagy to maintain mitochondrial structure and function. We investigated the role of the dynamin-like GTPase optic atrophy 1 (Opa1) in mitophagy following myocardial infarction. Opa1 expression was downregulated in infarcted hearts in vivo and in hypoxia-treated cardiomyocytes in vitro. We found that Opa1 overexpression protected cardiomyocytes against hypoxia-induced damage and enhanced cell viability by inducing mitophagy. Opa1-induced mitophagy was activated by treatment with irisin, which protected cardiomyocytes from further damage following myocardial infarction. Opa1 knockdown abolished the cardioprotective effects of irisin resulting in an enhanced inflammatory response, increased oxidative stress, and mitochondrial dysfunction in cardiomyocytes. Our data indicate that Opa1 plays an important role in maintaining cardiomyocyte viability and mitochondrial function following myocardial infarction by inducing mitophagy. Irisin can activate Opa1-induced...Continue Reading

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Citations

Sep 29, 2020·Frontiers in Cell and Developmental Biology·Ting XinFang Hu
Oct 18, 2020·International Journal of Molecular Sciences·Mirko PesceAntonia Patruno
Dec 3, 2020·Frontiers in Cell and Developmental Biology·Jia Zheng, Chengzhi Lu
Feb 11, 2021·International Journal of Molecular Sciences·Patrizia PignataroMaria Grano
Dec 16, 2020·International Journal of Molecular Sciences·Márton Richárd SzabóCsaba Csonka
Jun 6, 2021·Heart, Lung & Circulation·Yuntao HuZhibing Qiu
Jun 24, 2021·Journal of Cellular and Molecular Medicine·Chunfang WangDanyan Xu
Aug 28, 2021·International Journal of Molecular Sciences·Rosa MancinelliGiorgio Fanò-Illic
Oct 9, 2021·Journal of the American Heart Association·Jinjuan FuJian Yang

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Methods Mentioned

BETA
GTPase
PCR
flow cytometry
ELISA
transfection
enzyme-linked immunosorbent assay
ELISAs

Software Mentioned

FlowJo
GraphPad Prism
GraphPad

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