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The conserved microRNA miR-210 regulates lipid metabolism and photoreceptor maintenance in the Drosophila retina.

ABSTRACT: Increasing evidence suggests that miRNAs play important regulatory roles in the nervous system. However, the molecular mechanisms of how specific miRNAs affect neuronal development and functions remain less well understood. In the present study, we provide evidence that the conserved microRNA miR-210 regulates lipid metabolism and prevents neurodegeneration in the Drosophila retina. miR-210 is specifically expressed in the photoreceptor neurons and other sensory organs. Genetic deletion of miR-210 leads to lipid droplet accumulation and photoreceptor degeneration in the retina. These effects are associated with abnormal activation of the Drosophila sterol regulatory element-binding protein signaling. We further identify the acetyl-coenzyme A synthetase (ACS) as one functionally important target of miR-210 in this context. Reduction of ACS in the miR-210 mutant background suppresses the neurodegeneration defects, suggesting that miR-210 acts through regulation of the ACS transcript. Together, these results reveal an unexpected role of miR-210 in controlling lipid metabolism and neuronal functions.

SUBMITTER: Lyu J

PROVIDER: S-EPMC7862623 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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The conserved microRNA miR-210 regulates lipid metabolism and photoreceptor maintenance in the Drosophila retina.

Lyu Jialan J Chen Yuchen Y Yang Weiwei W Guo Ting T Xu Xiao X Xi Yongmei Y Yang Xiaohang X Ge Wanzhong W

Cell death and differentiation 20200910 2

Increasing evidence suggests that miRNAs play important regulatory roles in the nervous system. However, the molecular mechanisms of how specific miRNAs affect neuronal development and functions remain less well understood. In the present study, we provide evidence that the conserved microRNA miR-210 regulates lipid metabolism and prevents neurodegeneration in the Drosophila retina. miR-210 is specifically expressed in the photoreceptor neurons and other sensory organs. Genetic deletion of miR-2 ...[more]

PMID: 32913227

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Project description:BackgroundIschemic heart disease remains a leading cause of death worldwide. In this study, we test the hypothesis that microRNA-210 protects the heart from myocardial ischemia-reperfusion (IR) injury by controlling mitochondrial bioenergetics and reactive oxygen species (ROS) flux.MethodsMyocardial infarction in an acute setting of IR was examined through comparing loss- versus gain-of-function experiments in microRNA-210-deficient and wild-type mice. Cardiac function was evaluated by echocardiography. Myocardial mitochondria bioenergetics was examined using a Seahorse XF24 Analyzer.ResultsMicroRNA-210 deficiency significantly exaggerated cardiac dysfunction up to 6 weeks after myocardial IR in male, but not female, mice. Intravenous injection of microRNA-210 mimic blocked the effect and recovered the increased myocardial IR injury and cardiac dysfunction. Analysis of mitochondrial metabolism revealed that microRNA-210 inhibited mitochondrial oxygen consumption, increased glycolytic activity, and reduced mitochondrial ROS flux in the heart during IR injury. Inhibition of mitochondrial ROS with MitoQ consistently reversed the effect of microRNA-210 deficiency. Mechanistically, we showed that mitochondrial glycerol-3-phosphate dehydrogenase is a novel target of microRNA-210 in the heart, and loss-of-function and gain-of-function experiments revealed that glycerol-3-phosphate dehydrogenase played a key role in the microRNA-210-mediated effect on mitochondrial metabolism and ROS flux in the setting of heart IR injury. Knockdown of glycerol-3-phosphate dehydrogenase negated microRNA-210 deficiency-induced increases in mitochondrial ROS production and myocardial infarction and improved left ventricular fractional shortening and ejection fraction after the IR treatment.ConclusionsMicroRNA-210 targeting glycerol-3-phosphate dehydrogenase controls mitochondrial bioenergetics and ROS flux and improves cardiac function in a murine model of myocardial infarction in the setting of IR injury. The findings suggest new insights into the mechanisms and therapeutic targets for treatment of ischemic heart disease.

Dataset Information

The conserved microRNA miR-210 regulates lipid metabolism and photoreceptor maintenance in the Drosophila retina.

Publications

The conserved microRNA miR-210 regulates lipid metabolism and photoreceptor maintenance in the Drosophila retina.

Similar Datasets

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