The Hippo Pathway Orchestrates Mitochondrial Quality Control: A Novel Focus on Cardiovascular Diseases

2020 ◽  
Vol 39 (9) ◽  
pp. 1494-1505
Author(s):  
Ying Tan ◽  
Cai Lei ◽  
Huifang Tang ◽  
Xiao Zhu ◽  
Guanghui Yi
Keyword(s):  
Quality Control ◽  
Cardiovascular Diseases ◽  
Hippo Pathway ◽  
Mitochondrial Quality Control ◽  
The Hippo Pathway

Lactoferrin ameliorates pathological cardiac hypertrophy related to mitochondrial quality control in aged mice

2021 ◽  
Author(s):  
Lishan Huang ◽  
Ruiyu Chen ◽  
Libin Liu ◽  
Yu Zhou ◽  
Zhou Chen
Keyword(s):  
Quality Control ◽  
Cardiovascular Diseases ◽  
Cardiac Hypertrophy ◽  
Myocardial Hypertrophy ◽  
Treatment Strategies ◽  
The Elderly ◽  
Mitochondrial Quality Control ◽  
Effective Prevention ◽  
Pathological Cardiac Hypertrophy ◽  
Prevention And Treatment

Pathological myocardial hypertrophy, which lacks effective prevention and treatment strategies, makes the elderly susceptible to various cardiovascular diseases. Based on the beneficial attributes of lactoferrin in aging-related diseases, we aimed...

scholarly journals Regulation of Mitochondrial Quality Control by Natural Drugs in the Treatment of Cardiovascular Diseases: Potential and Advantages

2020 ◽  
Vol 8 ◽  
Author(s):  
Xing Chang ◽  
Wenjin Zhang ◽  
Zhenyu Zhao ◽  
Chunxia Ma ◽  
Tian Zhang ◽  
...  
Keyword(s):  
Quality Control ◽  
Cardiovascular Diseases ◽  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Therapeutic Effects ◽  
Active Ingredients ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Energy Metabolism ◽  
Natural Drugs ◽  
Mitochondrial Respiratory

Mitochondria are double-membraned cellular organelles that provide the required energy and metabolic intermediates to cardiomyocytes. Mitochondrial respiratory chain defects, structure abnormalities, and DNA mutations can affect the normal function of cardiomyocytes, causing an imbalance in intracellular calcium ion homeostasis, production of reactive oxygen species, and apoptosis. Mitochondrial quality control (MQC) is an important process that maintains mitochondrial homeostasis in cardiomyocytes and involves multi-level regulatory mechanisms, such as mitophagy, mitochondrial fission and fusion, mitochondrial energy metabolism, mitochondrial antioxidant system, and mitochondrial respiratory chain. Furthermore, MQC plays a role in the pathological mechanisms of various cardiovascular diseases (CVDs). In recent years, the regulatory effects of natural plants, drugs, and active ingredients on MQC in the context of CVDs have received significant attention. Effective active ingredients in natural drugs can influence the production of energy-supplying substances in the mitochondria, interfere with the expression of genes associated with mitochondrial energy requirements, and regulate various mechanisms of MQC modulation. Thus, these ingredients have therapeutic effects against CVDs. This review provides useful information about novel treatment options for CVDs and development of novel drugs targeting MQC.

scholarly journals Natural Antioxidants Improve the Vulnerability of Cardiomyocytes and Vascular Endothelial Cells under Stress Conditions: A Focus on Mitochondrial Quality Control

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Xing Chang ◽  
Zhenyu Zhao ◽  
Wenjin Zhang ◽  
Dong Liu ◽  
Chunxia Ma ◽  
...  
Keyword(s):  
Quality Control ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Vascular Endothelial Cells ◽  
Vascular Complications ◽  
Natural Antioxidants ◽  
Mitochondrial Morphology ◽  
Vascular Endothelial ◽  
Mitochondrial Quality Control ◽  
Main Site

Cardiovascular disease has become one of the main causes of human death. In addition, many cardiovascular diseases are accompanied by a series of irreversible damages that lead to organ and vascular complications. In recent years, the potential therapeutic strategy of natural antioxidants in the treatment of cardiovascular diseases through mitochondrial quality control has received extensive attention. Mitochondria are the main site of energy metabolism in eukaryotic cells, including myocardial and vascular endothelial cells. Mitochondrial quality control processes ensure normal activities of mitochondria and cells by maintaining stable mitochondrial quantity and quality, thus protecting myocardial and endothelial cells against stress. Various stresses can affect mitochondrial morphology and function. Natural antioxidants extracted from plants and natural medicines are becoming increasingly common in the clinical treatment of diseases, especially in the treatment of cardiovascular diseases. Natural antioxidants can effectively protect myocardial and endothelial cells from stress-induced injury by regulating mitochondrial quality control, and their safety and effectiveness have been preliminarily verified. This review summarises the damage mechanisms of various stresses in cardiomyocytes and vascular endothelial cells and the mechanisms of natural antioxidants in improving the vulnerability of these cell types to stress by regulating mitochondrial quality control. This review is aimed at paving the way for novel treatments for cardiovascular diseases and the development of natural antioxidant drugs.

scholarly journals The Emerging Role of FUNDC1-Mediated Mitophagy in Cardiovascular Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Liu ◽  
Yimei Li ◽  
Quan Chen
Keyword(s):  
Quality Control ◽  
Cardiovascular Diseases ◽  
Essential Role ◽  
Cellular Structures ◽  
Regulation Mechanism ◽  
Lipid Transfer ◽  
Stress Growth ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Dynamic

Mitochondria are highly dynamic organelles and play essential role in ATP synthase, ROS production, innate immunity, and apoptosis. Mitochondria quality control is critical for maintaining the cellular function in response to cellular stress, growth, and differentiation Signals. Damaged or unwanted mitochondria are selectively removed by mitophagy, which is a crucial determinant of cell viability. Mitochondria-associated Endoplasmic Reticulum Membranes (MAMs) are the cellular structures that connect the ER and mitochondria and are involved in calcium signaling, lipid transfer, mitochondrial dynamic, and mitophagy. Abnormal mitochondrial quality induced by mitophagy impairment and MAMs dysfunction is associated with many diseases, including cardiovascular diseases (CVDs), metabolic syndrome, and neurodegenerative diseases. As a mitophagy receptor, FUNDC1 plays pivotal role in mitochondrial quality control through regulation of mitophagy and MAMs and is closely related to the occurrence of several types of CVDs. This review covers the regulation mechanism of FUNDC1-mediated mitophagy and MAMs formation, with a particular focus on its role in CVDs.

scholarly journals Hsp70–Bag3 complex is a hub for proteotoxicity-induced signaling that controls protein aggregation

2018 ◽  
Vol 115 (30) ◽  
pp. E7043-E7052 ◽  
Author(s):  
Anatoli B. Meriin ◽  
Arjun Narayanan ◽  
Le Meng ◽  
Ilya Alexandrov ◽  
Xaralabos Varelas ◽  
...  
Keyword(s):  
Quality Control ◽  
Protein Aggregation ◽  
Heat Shock Protein 70 ◽  
Hippo Pathway ◽  
Control Cell ◽  
Cell Physiology ◽  
Adaptive Responses ◽  
Abnormal Protein ◽  
Proteotoxic Stress ◽  
The Hippo Pathway

Protein abnormalities in cells are the cause of major pathologies, and a number of adaptive responses have evolved to relieve the toxicity of misfolded polypeptides. To trigger these responses, cells must detect the buildup of aberrant proteins which often associate with proteasome failure, but the sensing mechanism is poorly understood. Here we demonstrate that this mechanism involves the heat shock protein 70–Bcl-2–associated athanogene 3 (Hsp70–Bag3) complex, which upon proteasome suppression responds to the accumulation of defective ribosomal products, preferentially recognizing the stalled polypeptides. Components of the ribosome quality control system LTN1 and VCP and the ribosome-associated chaperone NAC are necessary for the interaction of these species with the Hsp70–Bag3 complex. This complex regulates important signaling pathways, including the Hippo pathway effectors LATS1/2 and the p38 and JNK stress kinases. Furthermore, under proteotoxic stress Hsp70–Bag3–LATS1/2 signaling regulates protein aggregation. We established that the regulated step was the emergence and growth of abnormal protein oligomers containing only a few molecules, indicating that aggregation is regulated at very early stages. The Hsp70–Bag3 complex therefore functions as an important signaling node that senses proteotoxicity and triggers multiple pathways that control cell physiology, including activation of protein aggregation.

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