Role of Mitophagy in Coronary Heart Disease: Targeting the Mitochondrial Dysfunction and Inflammatory Regulation

Liu, Mingxuan; Wu, Ying

doi:10.3389/fcvm.2022.819454

Cited by 11 publications

(11 citation statements)

References 166 publications

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“…Playing a central role in metabolism, mitochondria are also key players in the regulation of the immune and inflammatory responses [ 32 ]. Several studies reported the immunogenic capabilities of dysfunctional mitochondria [ 7 , 33 ].…”

Section: Mitophagy In Immunitymentioning

confidence: 99%

The Role of Mitochondrial Mutations in Chronification of Inflammation: Hypothesis and Overview of Own Data

Orekhov

Nikiforov

Omelchenko

et al. 2022

Life

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Chronic human diseases, especially age-related disorders, are often associated with chronic inflammation. It is currently not entirely clear what factors are responsible for the sterile inflammatory process becoming chronic in affected tissues. This process implies impairment of the normal resolution of the inflammatory response, when pro-inflammatory cytokine production ceases and tissue repair process begins. The important role of the mitochondria in the correct functioning of innate immune cells is currently well recognized, with mitochondrial signals being an important component of the inflammatory response regulation. In this work, we propose a hypothesis according to which mitochondrial DNA (mtDNA) mutations may play a key role in rendering certain cells prone to prolonged pro-inflammatory activation, therefore contributing to chronification of inflammation. The affected cells become sites of constant pro-inflammatory stimulation. The study of the distribution of atherosclerotic lesions on the surface of the arterial wall samples obtained from deceased patients revealed a focal distribution of lesions corresponding to the distribution of cells with altered morphology that are affected by mtDNA mutations. These observations support the proposed hypothesis and encourage further studies.

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Section: Mitophagy In Immunitymentioning

confidence: 99%

The Role of Mitochondrial Mutations in Chronification of Inflammation: Hypothesis and Overview of Own Data

Orekhov

Nikiforov

Omelchenko

et al. 2022

Life

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“…Mitophagy prevents the accumulation of abnormal mitochondria, while the suppression of mitophagy could lead to cardiomyocyte dysfunction or even death [ 40 ]. Accumulating pieces of evidence have demonstrated that mitophagy is critically involved in the development of mitochondrial dysfunction in various settings [ 41 ]. Of note, mitochondria can repair themselves through the mitophagy system, by delivering damaged mitochondrial fragments to lysosomes, to reduce the destruction caused by mitochondrial damage to cells, including reducing oxidative stress of cells and restoring mitochondrial energy metabolism [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-130a-3p regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial ischemia/reperfusion injury

et al. 2023

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Understanding the complex pathogenesis in myocardial ischemia/reperfusion (I/R) injury (IRI) is an urgent problem in clinical trials. Increasing pieces of evidence have suggested that miRNAs are involved in the occurrence and development of heart diseases by regulating mitochondria-related gene expression. Mitochondria have been acknowledged as the key triggers of cardiac I/R injury. However, the potential impact of miR-130a on mitochondria remains unclear in myocardial IRI. Exploring the regulatory mechanism of miR-130a on mitochondria may provide a new target for IRI therapy. In the present study, we found that miR-130a significantly increased in acute myocardial infarction (AMI) patients and myocardial I/R rats. MiR-130a could downregulate the viability of cardiomyocytes and the knockdown of miR-130a could protect the viability of cardiomyocytes under hypoxia-reoxygenation (HR). Over-expression of miR-130a resulted in mitochondrial dysfunction. It was evidenced by decreases in mitochondrial ATP production, mitochondrial membrane potential (MMP), and an increase in reactive oxygen species (ROS) production. However, suppression of miR-130a could protect against mitochondrial damage, show elevation of mitochondrial ATP production rate and MMP, and reduce ROS production. We further explored the effect of miR-130a on the mitochondrial quality control (QMC) system by determining mitochondrial-protein-specific proteases and analyzed mitochondrial morphology by fluorescence imaging and electron microscopy, respectively. It was noted that miR-130a could suppress mitochondrial fusion and FUNDC1-mediated mitophagy to accelerate myocardial IRI. Moreover, we investigated the potential miR-130a targeted mitochondria-related genes to understand the regulatory mechanism of miR-130a in the setting of myocardial IRI. It was revealed that miR-130a targeted GJA1, and GJA1 rescued IRI by enhancing ATP production rate and oxidative phosphorylation, meanwhile protecting cell viability, MMP, and activating mitophagy. In addition, the knockdown of miR-130a significantly activated FUNDC1-mediated mitophagy, while the knockdown of GJA1 reversed the relevant response. Collectively, our findings suggest that miR-130a regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial IRI.

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“…Mitophagy prevents the accumulation of abnormal mitochondria, while the suppression of mitophagy could lead to cardiomyocyte dysfunction or even death (40). Accumulating evidences have demonstrated that mitophagy is critically involved in the development of mitochondrial dysfunction in various settings (41).…”

Section: Discussionmentioning

confidence: 99%

MiR-130a Regulates FUNDC1-Mediated Mitophagy by Targeting GJA1 in Myocardial Ischemia/Reperfusion Injury

Yan

Tian

Jia

et al. 2022

Preprint

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To understand the complex pathogenesis in myocardial ischemia/reperfusion (I/R) injury (IRI) is the urgent problem solved in clinical trials. Increasing evidences have suggested that miRNAs are involved in the occurrence and development of heart diseases by regulating the mitochondria-related genes expression. Mitochondria have been acknowledged as the key triggers of cardiac I/R injury. However, the potential impact of miR-130a on mitochondria remains unclear in myocardial IRI. Exploring the regulatory mechanism of miR-130a on mitochondria may provide a new target for IRI therapy. In the present study, we found that miR-130a was significantly increased in the acute myocardial infarction (AMI) patients and myocardial I/R rats. Over-expression of miR-130a resulted in mitochondrial dysfunction, evidenced by decreases in mitochondrial ATP production rate as well as mitochondrial membrane potential (MMP), and increase in reactive oxygen species (ROS) production. However, suppression of miR-130a could protect mitochondrial damage, showing elevation of mitochondrial ATP production rate and MMP, and reduction of ROS production. We further explored the effect of miR-130a on mitochondrial quality control (MQC) system by determining mitochondrial-protein-specific proteases, and mitochondrial morphology was analyzed by fluorescence imaging and electron microscopy, respectively. It was noted that miR-130a could obviously suppress mitochondrial fusion and FUNDC1-mediated mitophagy to accelerate myocardial IRI. Moreover, we investigated the potential miR-130a targetd mitochondria-related genes to understand the regulatory mechanism of miR-130a in the setting of myocardial IRI. It was revealed that miR-130a evidently targeted GJA1, and GJA1 rescued IRI through protecting MMP and activating mitophagy. In addition, knockdown of miR-130a significantly activated FUNDC1-mediated mitophagy, while knockdown of GJA1 reversed the relevant response. Collectively, our findings suggest that miR-130a regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial IRI.

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Role of Mitophagy in Coronary Heart Disease: Targeting the Mitochondrial Dysfunction and Inflammatory Regulation

Cited by 11 publications

References 166 publications

The Role of Mitochondrial Mutations in Chronification of Inflammation: Hypothesis and Overview of Own Data

The Role of Mitochondrial Mutations in Chronification of Inflammation: Hypothesis and Overview of Own Data

MiR-130a-3p regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial ischemia/reperfusion injury

MiR-130a Regulates FUNDC1-Mediated Mitophagy by Targeting GJA1 in Myocardial Ischemia/Reperfusion Injury

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