Mitophagy Disequilibrium, a Prominent Pathological Mechanism in Metabolic Heart Diseases

Li, Yunhao; Zheng, Ningning; Ding, Xiwei

doi:10.2147/dmso.s336882

Cited by 11 publications

(9 citation statements)

References 110 publications

(100 reference statements)

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“…The role of mitophagy and its underlying mechanisms in the diabetic heart remain largely unknown [ 107 ]. PINK1/Parkin pathway is inhibited in the hearts of various diabetic animals, indicating that mitophagy is closely related to diabetic hearts [ 108 ]. Beclin 1 or Atg 16L1 deficient mice could restore the PINK1/Parkin pathway, alleviating diabetic heart function [ 109 ].…”

Section: Mitochondrial Signaling In Metabolic Syndrome-related Cardio...mentioning

confidence: 99%

The Role of Mitochondria in Metabolic Syndrome–Associated Cardiomyopathy

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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With the rapid development of society, the incidence of metabolic syndrome (MS) is increasing rapidly. Evidence indicated that patients diagnosed with MS usually suffered from cardiomyopathy, called metabolic syndrome–associated cardiomyopathy (MSC). The clinical characteristics of MSC included cardiac hypertrophy and diastolic dysfunction, followed by heart failure. Despite many studies on this topic, the detailed mechanisms are not clear yet. As the center of cellular metabolism, mitochondria are crucial for maintaining heart function, while mitochondria dysfunction plays a vital role through mechanisms such as mitochondrial energy deprivation, calcium disorder, and ROS (reactive oxygen species) imbalance during the development of MSC. Accordingly, in this review, we will summarize the characteristics of MSC and especially focus on the mechanisms related to mitochondria. In addition, we will update new therapeutic strategies in this field.

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Section: Mitochondrial Signaling In Metabolic Syndrome-related Cardio...mentioning

confidence: 99%

The Role of Mitochondria in Metabolic Syndrome–Associated Cardiomyopathy

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…12 Presently, there exist two principal regulatory pathways that regulate the process of mitophagy: The first is mitophagy chiefly overseen by PTEN-induced putative kinase 1 (PINK1)/cytoplasmic E3 ubiquitin ligase (Parkin) and non-Parkindependent ubiquitin-dependent mitophagy; The second refers to mitophagy mediated by mitophagy receptors, that is, non-ubiquitindependent mitophagy. 13 These mitophagy receptors are usually mitochondrial proteins containing the microtubule-associated protein…”

Section: Mitophagy Pathways In Msmentioning

confidence: 99%

“…Mitophagy can be triggered through a variety of pathways, such as nutritional deficiency (starvation), disruption of the mitochondrial membrane potential, respiratory depression, hypoxia, and ROS accumulation 12 . Presently, there exist two principal regulatory pathways that regulate the process of mitophagy: The first is mitophagy chiefly overseen by PTEN‐induced putative kinase 1 (PINK1)/cytoplasmic E3 ubiquitin ligase (Parkin) and non‐Parkin‐dependent ubiquitin‐dependent mitophagy; The second refers to mitophagy mediated by mitophagy receptors, that is, non‐ubiquitin‐dependent mitophagy 13 . These mitophagy receptors are usually mitochondrial proteins containing the microtubule‐associated protein 1 light chain 3 (LC3)/GABARAP‐interacting region (LIR) motif, which can regulates the formation of mitochondrial isolation membranes through specific binding of LIR to members of the mitochondrial Atg8 family (LC3A/B/C, GABARAP, GABARAP‐L1/2).…”

Section: Mitophagy Pathways In Msmentioning

confidence: 99%

Mitophagy in metabolic syndrome

Miao

Han

Liu

2023

J of Clinical Hypertension

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Metabolic syndrome (MS), a chronic and non‐communicable pathological condition, is characterized by a constellation of clinical manifestations including insulin resistance, abdominal adiposity, elevated blood pressure, and perturbations in lipid metabolism. The prevalence of MS has increased dramatically in both developed and developing countries and has now become a truly global problem. Excessive energy intake and concomitant obesity are the main drivers of this syndrome. Mitophagy, in which cells degrade damaged mitochondria through a selective form of autophagy, assumes a crucial position in the regulation of mitochondrial integrity and maintenance. Abnormal mitochondrial quality could result in a spectrum of pathological conditions related to metabolic dysfunction, including metabolic syndrome, cardiovascular ailments, and neoplasms. Recently, there has been a proliferation of research pertaining to the process of mitophagy in the context of MS, and there are various regulatory pathways in MS, including pathways like the ubiquitin‐dependent mechanism and receptor‐mediated mechanisms, among others. Furthermore, studies have uncovered that the process of mitophagy serves a defensive function in the advancement of Metabolic Syndrome, and inhibition of mitophagy exacerbates the advancement of MS. As a result, the regulation of mitophagy holds great promise as a therapeutic approach in the management of Metabolic Syndrome. In this comprehensive analysis, the authors present a synthesis of the diverse regulatory pathways involved in mitophagy in the context of Metabolic Syndrome, as well as its modes of action in metabolic disorders implicated in the development of MS, Including obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM), offering novel avenues for the prophylaxis and therapeutic management of MS.

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“…Torin 1, Drp, MFN, Pink, and Parkin are all known to be key mediators of cell growth. [19][20][21][22][23] In addition, these proteins are closely associated with cell autophagy. 24,25 Meanwhile, it was reported that Puerarin can inhibit autophagy.…”

Section: Introductionmentioning

confidence: 99%

Puerarin Alleviates LPS-Induced H9C2 Cell Injury by Inducing Mitochondrial Autophagy

Chang

Luo

et al. 2022

Journal of Cardiovascular Pharmacology

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Sepsis leads to the damage of multiple organs, and thereby adversely affects the cardiovascular system. At present, no effective method has been found to treat myocardial injury caused by sepsis. Although Puerarin was reported to attenuate lipopolysaccharide (LPS)-induced mitochondrial injury in H9C2 cells, the effects of Puerarin in sepsis-induced myocardial injury remain unclear. In this study, H9C2 cells were stimulated with LPS, CCK-8 assays were performed to assess cell viability, and flow cytometry and TUNEL staining were used to assess cell apoptosis. Levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and enzyme activity were investigated using commercial kits. Reactive oxygen species (ROS) levels in H9C2 cells were detected by flow cytometry. Autophagosomes in the mitochondria of H9C2 cells were observed by transmission electron microscope, and protein expression was assessed by western blotting. Furthermore, in vivo experiments were applied to test the function of Puerarin in sepsis. We found that Puerarin significantly reversed LPS-induced decreases in H9C2 cell viability by inhibiting apoptosis. The ROS levels in H9C2 cells were significantly upregulated by LPS, but that effect was markedly reduced by Puerarin. In addition, Puerarin attenuated LPS-induced mitochondrial injury in H9C2 cells by regulating dynamin-related protein 1 (Drp1) and mitofusin 1 (MFN1). LPS decreased enzyme activity and reduced the levels of ADP, ALP, and AMP in mitochondria; however, those effects were reversed by Puerarin. Puerarin and Torin1 reversed LPSinduced inhibition of autophagy in the mitochondria of H9C2 cells via mediation of p62, LC3B, Pink1, and Parkin. Puerarin notably inhibited the progression of sepsis in vivo. Puerarin inhibited LPSinduced H9C2 cell injury by inducing mitochondrial autophagy, which acts as a mechanism for preventing myocardial injury caused by sepsis.

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Mitophagy Disequilibrium, a Prominent Pathological Mechanism in Metabolic Heart Diseases

Cited by 11 publications

References 110 publications

The Role of Mitochondria in Metabolic Syndrome–Associated Cardiomyopathy

The Role of Mitochondria in Metabolic Syndrome–Associated Cardiomyopathy

Mitophagy in metabolic syndrome

Puerarin Alleviates LPS-Induced H9C2 Cell Injury by Inducing Mitochondrial Autophagy

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