Mitochondrial CHCHD2: Disease-Associated Mutations, Physiological Functions, and Current Animal Models

Rare mutations in the mitochondrial protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) are associated with Parkinson’s disease (PD) and other Lewy body disorders. CHCHD2 is a bi-organellar mediator of oxidative phosphorylation, playing crucial roles in regulating electron flow in the mitochondrial electron transport chain and acting as a nuclear transcription factor for a cytochrome c oxidase subunit (COX4I2) and itself in response to hypoxic stress. CHCHD2 also regulates cell migration and differentiation, mitochondrial cristae structure, and apoptosis. In this review, we summarize the known disease-associated mutations of CHCHD2 in Asian and Caucasian populations, the physiological functions of CHCHD2, how CHCHD2 mutations contribute to α-synuclein pathology, and current animal models of CHCHD2. Further, we discuss the necessity of continued investigation into the divergent functions of CHCHD2 and CHCHD10 to determine how mutations in these similar mitochondrial proteins contribute to different neurodegenerative diseases.

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Effect of short- and long-term phosphate stress on the non-phosphorylating pathway of mitochondrial electron transport in Arabidopsis thaliana

Functional Plant Biology ◽

10.1071/fp09206 ◽

2010 ◽

Vol 37 (5) ◽

pp. 455 ◽

Cited By ~ 9

Author(s):

Vivek Vijayraghavan ◽

Kathleen Soole

Keyword(s):

Arabidopsis Thaliana ◽

Electron Transport ◽

Electron Transport Chain ◽

Electron Flow ◽

Mitochondrial Electron Transport Chain ◽

Short Term ◽

Transport Chain ◽

Short And Long Term ◽

Pi Stress

Wild-type Arabidopsis thaliana L. seedlings generated in liquid culture were subjected to long- and short-term phosphate (Pi) stress to assess the response of the non-phosphorylating pathway of mitochondrial electron transport, comprising the internal (NDin) and external (NDex) non-phosphorylating NAD(P)H dehydrogenases and the alternative oxidase (AOX). Tissue Pi levels decreased but anthocyanin levels increased in both short- and long-term Pi stress. Oxidative damage was either lower or unchanged in response to short- and long-term Pi term stress. NDin and AOX capacity were elevated only in response to long-term Pi stress whereas NDex capacity was elevated only in response to short-term Pi stress. The only ND genes with elevated transcript levels in response to both short- and long-term Pi stress were Atnda2 (an NDin) and Atndb2 (an NDex). The binding site for PHR1, a transcription factor involved in the Pi stress response, was found in the promoter regions of Atnda2 and Atndb2. Results of this study indicate that a non-phosphorylating mitochondrial electron transport chain consisting of NDA2, NDB2 and AOX is synthesised to maintain respiratory electron flow through the mitochondrial electron transport chain during Pi stress.

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Bibliometrics and Visualization of the Mechanisms of Parkinson's Diseases Based on Animal Models

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200421103429 ◽

2020 ◽

Vol 20 (10) ◽

pp. 1560-1568 ◽

Cited By ~ 1

Author(s):

Yan-Qiu Wang ◽

Yi-Bing Chen ◽

Dong Xu ◽

Yuan-Lu Cui

Keyword(s):

Oxidative Stress ◽

Animal Models ◽

Mitochondrial Protein ◽

Bibliometric Method ◽

Metabolism Disorder ◽

Parkinson’S Diseases ◽

Model Drug ◽

6 Hydroxydopamine ◽

Rats And Mice ◽

Energy Metabolism Disorder

Objective: Energy metabolism disorder is one of the causes of Parkinson's disease (PD). Rodents, such as rats and mice are often used to establish animal models of PD. This paper used a bibliometric method to analyze the studies of rat and mouse PD models published between 2009 and 2018 in the Web of Science (WOS) database using CiteSpace V software. In addition, we conducted a literature review on the development status and research hotspots in this field in the past ten years. Methods: The related articles on rat and mouse PD models were retrieved from the WOS database, and an analysis of the keywords in these articles was conducted using CiteSpace V. A timeline graph was developed by the software in order to show the focus of researchers in the PD field. Results : A total of 8,636 articles were obtained. Results of the cluster analysis in the PD field such as neuroinflammation, oxidative stress, and autophagy, contributed to the systematic review about the pathogenesis of PD. At the same time, based on the property of the model drug, this review has summarized and compared different administration techniques and mechanisms of 6-hydroxydopamine (6- OHDA), 1-methyl-4-phenyl-1, 2, 4, 5-tetrahydropyridine (MPTP), paraquat and rotenone. Conclusion: According to the bibliometric analysis, studies on PD were focused on the mechanisms of oxidative stress, neuroinflammation, and autophagy. Activated microglia releases inflammatory cytokines; mitochondrial dysfunction is caused by oxidative damage of mitochondrial protein; abnormal autophagy-lysosome pathway can lead to abnormal protein deposition in dopaminergic neurons. In addition, although many animal models of PD have been established, there are some limitations of such models. Therefore, it is necessary to develop models that accurately mimic human PD.

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AB0031 T HELPER 17 CELLS WERE SIGNIFICANTLY DECREASED BY MITOCHONDRIAL ELECTRON TRANSPORT CHAIN COMPLEX INHIBITOR IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3441 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1318.2-1318

Author(s):

H. R. Lee ◽

S. J. Yoo ◽

J. Kim ◽

I. S. Yoo ◽

C. K. Park ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Electron Transport ◽

Disease Activity ◽

Th17 Cells ◽

Electron Transport Chain ◽

Chain Complex ◽

Complex Iii ◽

Mitochondrial Electron Transport Chain ◽

Transport Chain ◽

Healthy Control

Background:Reactive oxygen species (ROS) and T helper 17 (TH17) cells have been known to play an important role in the pathogenesis of rheumatoid arthritis (RA). However, the interrelationship between ROS and TH17 remains unclear in RAObjectives:To explore whether ROS affect TH17 cells in peripheral blood mononuclear cells (PBMC) of RA patients, we analyzed ROS expressions among T cell subsets following treatment with mitochondrial electron transport chain complex inhibitors.Methods:Blood samples were collected from 40 RA patients and 10 healthy adult volunteers. RA activity was divided according to clinical parameter DAS28. PBMC cells were obtained from the whole blood using lymphocyte separation medium density gradient centrifugation. Following PBMC was stained with Live/Dead stain dye, cells were incubated with antibodies for CD3, CD4, CD8, and CD25. After fixation and permeabilization, samples were stained with antibodies for FoxP3 and IL-17A. MitoSox were used for mitochondrial specific staining.Results:The frequency of TH17 cells was increased by 4.83 folds in moderate disease activity group (5.1>DAS28≥3.2) of RA patients compared to healthy control. Moderate RA activity patients also showed higher ratio of TH17/Treg than healthy control (3.57 folds). All RA patients had elevated expression of mitochondrial specific ROS than healthy control. When PBMC cells were treated with 2.5uM of antimycin A (mitochondrial electron transport chain complex III inhibitor) for 16 h, the frequency of TH17 cells was significantly decreased.Conclusion:The mitochondrial electron transport chain complex III inhibitor markedly downregulated the frequency of TH17 cells in moderate disease activity patients with RA. These findings provide a novel approach to regulate TH17 function in RA through mitochondrial metabolism related ROS production.References:[1]Szekanecz, Z., et al., New insights in synovial angiogenesis. Joint Bone Spine, 2010. 77(1): p. 13-9.[2]Prevoo, M.L., et al., Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum, 1995. 38(1): p. 44-8.Disclosure of Interests:None declared

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Regulation of Cytochrome c Oxidase by Natural Compounds Resveratrol, (–)-Epicatechin, and Betaine

Cells ◽

10.3390/cells10061346 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1346

Author(s):

Icksoo Lee

Keyword(s):

Cytochrome C ◽

Cytochrome C Oxidase ◽

Model Systems ◽

Health Improvement ◽

Published Data ◽

Mitochondrial Electron Transport Chain ◽

Naturally Occurring ◽

Transport Chain ◽

Wide Range ◽

Experimental Model Systems

Numerous naturally occurring molecules have been studied for their beneficial health effects. Many compounds have received considerable attention for their potential medical uses. Among them, several substances have been found to improve mitochondrial function. This review focuses on resveratrol, (–)-epicatechin, and betaine and summarizes the published data pertaining to their effects on cytochrome c oxidase (COX) which is the terminal enzyme of the mitochondrial electron transport chain and is considered to play an important role in the regulation of mitochondrial respiration. In a variety of experimental model systems, these compounds have been shown to improve mitochondrial biogenesis in addition to increased COX amount and/or its enzymatic activity. Given that they are inexpensive, safe in a wide range of concentrations, and effectively improve mitochondrial and COX function, these compounds could be attractive enough for possible therapeutic or health improvement strategies.

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