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

Xing Chang,Zhenyu Zhao,Tian Zhang,Wenjin Zhang,Lei Zhang,Qingyan Meng,Yuping Zhao,Peizheng Yan,Chunxia Ma

doi:10.3389/fcell.2020.616139

Abstract

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.

Highlights

Cardiovascular diseases (CVDs) are among the primary causes of death worldwide
These findings show that Periplaneta americana Extract (PAE) regulates mitophagy through the PTEN-induced kinase 1 (PINK1)/parkin pathway and protects cardiomyocytes from injury
Astragaloside IV (AST) significantly upregulates the expression of B-cell lymphoma 2 (Bcl-2), in the mitochondria of cardiomyocytes, and inhibits mitochondrial reactive oxygen species (ROS) generation, maintains membrane potential (MMP), regulates mitochondrial permeability transition pores (mPTPs) opening, inhibits H9c2 cardiomyocyte apoptosis, promotes the recovery of rat myocardial function, and reduces the area of myocardial infarction. These results suggest that AST may modulate Mitochondrial quality control (MQC) by upregulating Bcl-2 and promoting its translocation to mitochondria, maintaining MMP, and inhibiting the cascade events induced by ROS, preventing mPTP opening, inhibiting cardiomyocyte opening, and alleviating myocardial injury

Summary

Introduction

Cardiovascular diseases (CVDs) are among the primary causes of death worldwide. Studies have shown that mitochondrial quality control (MQC) plays a key role in the treatment of CVDs (Li et al, 2020). Mitochondria are important semi-autonomous, double-membraned organelles, playing various regulatory roles in cell energy metabolism, signal transduction, reactive oxygen species (ROS) production, and apoptosis The mitochondria can determine the survival and death of cells, Mitochondrial Quality and Cardiovascular Diseases provide cellular energy through oxidative phosphorylation, and regulate the homeostasis of Ca2+, iron, and electrolytes (Tian L. et al, 2019). As the regulatory center of apoptosis, mitochondria can release apoptotic factors following stimulation by apoptosis signals, trigger caspase-dependent or caspaseindependent apoptosis pathways, and induce programmed cell death (Kordalewska and Markuszewski, 2015)

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Conclusion