scholarly journals Mitochondrial Quality Control in Cardiomyocytes: A Critical Role in the Progression of Cardiovascular Diseases

2020 ◽  
Vol 11 ◽  
Author(s):  
Hualin Fan ◽  
Zhengjie He ◽  
Haofeng Huang ◽  
Haixia Zhuang ◽  
Hao Liu ◽  
...  
Keyword(s):  
Quality Control ◽  
Cardiovascular Diseases ◽  
Critical Role ◽  
Mitochondrial Quality Control

scholarly journals Receptor-mediated mitophagy regulates EPO production and protects against renal anemia

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Guangfeng Geng ◽  
Jinhua Liu ◽  
Changlu Xu ◽  
Yandong yan Pei ◽  
Linbo Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Quality Control ◽  
Therapeutic Strategy ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Renal Anemia ◽  
Inflammatory Factors ◽  
Oxygen Species ◽  
Mitochondrial Quality Control ◽  
Hematopoietic Disorders

Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive. In this study, we showed that FUNDC1, a mitophagy receptor, plays a critical role in EPO-driven erythropoiesis induced by stresses. Mechanistically, EPO production is impaired in REPs in Fundc1-/- mice upon stresses, and the impairment is caused by the accumulation of damaged mitochondria, which consequently leads to the elevation of the reactive oxygen species (ROS) level and triggers inflammatory responses by up-regulating proinflammatory cytokines. These inflammatory factors promote the myofibroblastic transformation of REPs, resulting in the reduction of EPO production. We therefore provide a link between aberrant mitophagy and deficient EPO generation in renal anemia. Our results also suggest that the mitochondrial quality control safeguards REPs under stresses, which may serve as a potential therapeutic strategy for the treatment of renal anemia.

scholarly journals Mieap forms membraneless organelles to compartmentalize and facilitate cardiolipin metabolism

2020 ◽  
Author(s):  
Naoki Ikari ◽  
Katsuko Honjo ◽  
Yoko Sagami ◽  
Yasuyuki Nakamura ◽  
Hirofumi Arakawa
Keyword(s):  
Quality Control ◽  
Critical Role ◽  
Enzymatic Reactions ◽  
Liquid Droplets ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Quality Control ◽  
Kidney Mitochondria ◽  
Intrinsically Disordered ◽  
Liver And Kidney ◽  
Inducible Protein

AbstractLiquid droplets function as membraneless organelles that compartmentalize and facilitate efficient biological reactions in cells. They are formed by proteins with an intrinsically disordered region(s) (IDR) via liquid–liquid phase separation. Mieap/SPATA18, a p53-inducible protein, plays a critical role in the suppression of human and murine colorectal tumors via mitochondrial quality control. However, the regulatory mechanism underlying this process remains unclear. Here, we report that Mieap is an IDR-containing protein that drives the formation of liquid droplets in the mitochondria. Mieap liquid droplets (MLDs) specifically phase separate the mitochondrial phospholipid cardiolipin. Lipidomic analysis of cardiolipin suggested that Mieap promotes enzymatic reactions involved in cardiolipin metabolism, including biosynthesis and remodeling. Accordingly, four cardiolipin biosynthesis enzymes, TAMM41, PGS1, PTPMT1, and CRLS1, and two remodeling enzymes, PLA2G6 and TAZ, are phase separated by MLDs. Mieap-deficient mice exhibited altered cristae structure in the liver and kidney mitochondria and a trend of obesity. These results suggest that Mieap drives the formation of membraneless organelles to compartmentalize and promotes cardiolipin metabolism at the inner mitochondrial membrane, thus playing a possible role in mitochondrial quality control.

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 Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 179
Author(s):  
Brian Pak Shing Pang ◽  
Wing Suen Chan ◽  
Chi Bun Chan
Keyword(s):  
Skeletal Muscle ◽  
Quality Control ◽  
Control System ◽  
Energy Content ◽  
Mitochondrial Dynamics ◽  
Critical Role ◽  
Oxidative Capacity ◽  
Quality Control System ◽  
Mitochondrial Quality Control ◽  
Tissue Mass

Mitochondria are the cellular powerhouses that generate adenosine triphosphate (ATP) to substantiate various biochemical activities. Instead of being a static intracellular structure, they are dynamic organelles that perform constant structural and functional remodeling in response to different metabolic stresses. In situations that require a high ATP supply, new mitochondria are assembled (mitochondrial biogenesis) or formed by fusing the existing mitochondria (mitochondrial fusion) to maximize the oxidative capacity. On the other hand, nutrient overload may produce detrimental metabolites such as reactive oxidative species (ROS) that wreck the organelle, leading to the split of damaged mitochondria (mitofission) for clearance (mitophagy). These vital processes are tightly regulated by a sophisticated quality control system involving energy sensing, intracellular membrane interaction, autophagy, and proteasomal degradation to optimize the number of healthy mitochondria. The effective mitochondrial surveillance is particularly important to skeletal muscle fitness because of its large tissue mass as well as its high metabolic activities for supporting the intensive myofiber contractility. Indeed, the failure of the mitochondrial quality control system in skeletal muscle is associated with diseases such as insulin resistance, aging, and muscle wasting. While the mitochondrial dynamics in cells are believed to be intrinsically controlled by the energy content and nutrient availability, other upstream regulators such as hormonal signals from distal organs or factors generated by the muscle itself may also play a critical role. It is now clear that skeletal muscle actively participates in systemic energy homeostasis via producing hundreds of myokines. Acting either as autocrine/paracrine or circulating hormones to crosstalk with other organs, these secretory myokines regulate a large number of physiological activities including insulin sensitivity, fuel utilization, cell differentiation, and appetite behavior. In this article, we will review the mechanism of myokines in mitochondrial quality control and ROS balance, and discuss their translational potential.

scholarly journals Culling sick mitochondria from the herd

2010 ◽  
Vol 191 (7) ◽  
pp. 1225-1227 ◽  
Author(s):  
Leo J. Pallanck
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Critical Role ◽  
Mitochondrial Fusion ◽  
Mitochondrial Quality Control ◽  
Endoplasmic Reticulum Associated Degradation ◽  
Cell Biol

The PINK1–Parkin pathway plays a critical role in mitochondrial quality control by selectively targeting damaged mitochondria for autophagy. In this issue, Tanaka et al. (2010. J. Cell Biol. doi: 10.1083/jcb.201007013) demonstrate that the AAA-type ATPase p97 acts downstream of PINK1 and Parkin to segregate fusion-incompetent mitochondria for turnover. p97 acts by targeting the mitochondrial fusion-promoting factor mitofusin for degradation through an endoplasmic reticulum–associated degradation (ERAD)-like mechanism.

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 Decreasing pdzd8-mediated mitochondrial-ER contacts in neurons improves fitness by increasing mitophagy

2020 ◽  
Author(s):  
Victoria L. Hewitt ◽  
Leonor Miller-Fleming ◽  
Simonetta Andreazza ◽  
Francesca Mattedi ◽  
Julien Prudent ◽  
...  
Keyword(s):  
Quality Control ◽  
Healthy Aging ◽  
Synapse Formation ◽  
Critical Role ◽  
Functional Characterization ◽  
Protective Effects ◽  
Mitochondrial Quality Control ◽  
Age Related ◽  
The Many

AbstractThe complex cellular architecture of neurons combined with their longevity makes maintaining a healthy mitochondrial network particularly important and challenging. One of the many roles of mitochondrial-ER contact sites (MERCs) is to mediate mitochondrial quality control through regulating mitochondrial turn over. Pdzd8 is a newly discovered MERC protein, the organismal functions of which have not yet been explored. Here we identify and provide the first functional characterization of the Drosophila melanogaster ortholog of Pdzd8. We find that reducing pdzd8-mediated MERCs in neurons slows age-associated decline in locomotor activity and increases lifespan in Drosophila. The protective effects of pdzd8 knockdown in neurons correlate with an increase in mitophagy, suggesting that increased mitochondrial turnover may support healthy aging of neurons. In contrast, increasing MERCs by expressing a constitutive, synthetic ER-mitochondria tether disrupts mitochondrial transport and synapse formation, accelerates age-related decline in locomotion and reduces lifespan. We also show that depletion of pdzd8 rescues the locomotor defects characterizing an Alzheimer’s disease (AD) fly model over-expressing Amyloidβ1–42 (Aβ42) and prolongs the survival of flies fed with mitochondrial toxins. Together, our results provide the first in vivo evidence that MERCs mediated by the tethering protein pdzd8 play a critical role in the regulation of mitochondrial quality control and neuronal homeostasis.

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.

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