scholarly journals Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
MengJie Hu ◽  
Keith E Schulze ◽  
Reena Ghildyal ◽  
Darren C Henstridge ◽  
Jacek L Kolanowski ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Quantitative Imaging ◽  
Virus Production ◽  
Dynein Motor ◽  
Mitochondrial Ros ◽  
Syncytial Virus ◽  
First Time

Although respiratory syncytial virus (RSV) is responsible for more human deaths each year than influenza, its pathogenic mechanisms are poorly understood. Here high-resolution quantitative imaging, bioenergetics measurements and mitochondrial membrane potential- and redox-sensitive dyes are used to define RSV’s impact on host mitochondria for the first time, delineating RSV-induced microtubule/dynein-dependent mitochondrial perinuclear clustering, and translocation towards the microtubule-organizing centre. These changes are concomitant with impaired mitochondrial respiration, loss of mitochondrial membrane potential and increased production of mitochondrial reactive oxygen species (ROS). Strikingly, agents that target microtubule integrity the dynein motor protein, or inhibit mitochondrial ROS production strongly suppresses RSV virus production, including in a mouse model with concomitantly reduced virus-induced lung inflammation. The results establish RSV’s unique ability to co-opt host cell mitochondria to facilitate viral infection, revealing the RSV-mitochondrial interface for the first time as a viable target for therapeutic intervention.

Abstract 403: FAM210A Maintains Cardiac Mitochondrial Homeostasis Through Regulating Letm1-dependent Ca 2+ Efflux

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Jiangbin Wu ◽  
Chinna Venkata ◽  
Si Chen ◽  
Omar Hedaya ◽  
Chen Yan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Membrane Potential ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Respiratory Activity ◽  
Genome Wide Association Studies ◽  
Ros Production ◽  
Mitochondrial Homeostasis ◽  
Mitochondrial Ros

Mitochondria play fundamental roles in supporting healthy myocardium function. Disturbed cardiac mitochondrial homeostasis causes mitochondrial dysfunction associated with cardiomyopathy in humans and mice. Recent genome-wide association studies (GWAS) discovered that the mutations of FAM210A (family with sequence similarity 210 member A) are associated with sarcopenia and osteoporosis. Interestingly, Fam210a is most highly expressed in the heart and multiple omics analyses in mouse hearts reveal Fam210a as a hub gene in cardiac hypertrophy. However, the molecular function of FAM210A in the heart remains elusive. Here, we discover that FAM210A is critical for maintaining cardiac mitochondrial function and homeostasis. Cardiomyocyte (CM) specific knockout (KO) of Fam210a in adult mice leads to progressive heart failure with enlarged left ventricle chamber and ultimately causes mortality at ~70 days after Fam210a KO. The FAM210A deficient CMs exhibit myofilament disarray at ~9 weeks post Fam210a KO. Moreover, Fam210a KO results in a remarkably elevated mitochondrial ROS production, dramatically compromised mitochondrial membrane potential, and reduced expression of mitochondrial electron transport chain (ETC) complex genes. As a result, the mitochondrial respiratory activity is significantly reduced and the mitochondrial cristae are disrupted in Fam210a KO CMs. In contrast, at the early stage of ~5 weeks post tamoxifen-induced Fam210a KO, we observe increased mitochondrial ROS production, disturbed mitochondrial membrane potential, and reduced respiratory activity in CMs prior to heart failure. Transcriptomic and proteomic analyses from Fam210a KO hearts indicate that FAM210A deficiency causes chronic integrated stress response (ISR) in the heart. Mechanistically, Interactome analyses show that FAM210A binds to mitochondrial Ca 2+ /H + exchanger LETM1 (leucine zipper and EF-hand containing transmembrane protein 1) and regulates LETM1-mediated mitochondrial Ca 2+ efflux. Altogether, we discover a novel function of FAM210A in maintaining the cardiac mitochondrial homeostasis by regulating mitochondrial Ca 2+ efflux, and deficiency of FAM210A causes mitochondrial dysfunction and leads to heart failure.

Cervicare™ induces apoptosis in HeLa and CaSki cells through ROS production and loss of mitochondrial membrane potential

RSC Advances ◽  
2016 ◽  
Vol 6 (29) ◽  
pp. 24391-24417 ◽  
Author(s):  
Neda Amini ◽  
Fadzilah Adibah Abdul Majid ◽  
Mohsen Marvibaigi ◽  
Eko Supriyanto ◽  
Saravana Kumar Jaganathan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Ros Production ◽  
Aqueous Extracts ◽  
Herbal Preparation ◽  
Proliferation And Apoptosis ◽  
First Time

The effect of the ethanol and aqueous extracts of Cervicare™, a poly-herbal preparation comprised of the combination of 6 plants, on cell proliferation and apoptosis using cervical cancer HeLa and CaSki cells was investigated for the first time in the present study.

Platelets apoptosis in rats after global brain ischemia

2018 ◽  
pp. 27-35
Author(s):  
А.А. Соколовская ◽  
Э.Д. Вирюс ◽  
В.В. Александрин ◽  
А.С. Роткина ◽  
К.А. Никифорова ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ischemic Stroke ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Brain Ischemia ◽  
Mitochondrial Membrane ◽  
Male Rats ◽  
Global Brain Ischemia ◽  
Platelet Apoptosis ◽  
Global Brain

Цель исследования. Ишемические повреждения головного мозга, являются одной из наиболее частой причин инвалидности и смертности во всем мире. Недавно была установлена роль апоптоза тромбоцитов в патофизиологии инсульта, однако его механизмы до сих пор остаются невыясненными. Несмотря на различные экспериментальные модели, направленные на мониторинг апоптоза тромбоцитов, результаты, относительно изучения и выявления апоптоза тромбоцитов при ишемии головного мозга у крыс, весьма немногочисленны. Цель исследования - анализ апоптоза тромбоцитов с помощью метода проточной цитофлуориметрии на модели глобальной ишемии мозга у крыс. Методика. В экспериментах использовано 6 крыс-самцов Вистар в возрасте от 5 до 6 мес., разделенных на 2 группы: интактный контроль (К) и глобальная ишемия головного мозга. Модель глобальной ишемии головного мозга у крыс воспроизводилась путём билатеральной окклюзии общих сонных артерий на фоне гипотензии. Уровень системного артериального давления снижали посредством кровопотери до 40-45 мм рт. ст. Суспензию тромбоцитов крыс получали методом гельфильтрации с использованием сефарозы 2B. Для анализа экстернализации фосфатидилсерина (ФС) тромбоциты крыс инкубировали с Аннексином V-PE в связывающем буфере. Для оценки митохондриального мембранного потенциала (ММП) тромбоциты инкубировали с катионным красителем JC-1. После инкубации образцы немедленно анализировали на проточном цитофлуориметре FACSCalibur (Becton Dickinson, США). Результаты. Согласно полученным данным, экстернализация ФС на тромбоцитах крыс, перенесших инсульт, была значительно выше (53,45 ± 4,21%), чем в контрольной группе крыс (5,27 ± 2,40%). Данный эффект подтверждается выраженной деполяризацией митохондриальных мембран (DYm). После экспериментальной ишемии мозга почти 40% тромбоцитов было деполяризовано. Заключение. Использованный в работе подбор методов и маркеров обеспечивает понимание механизмов апоптоза тромбоцитов как в экспериментальных, так и в клинических условиях. Полученные данные позволяют сделать заключение, что апоптоз тромбоцитов является одним из факторов развития глобальной ишемии головного мозга у крыс. Результаты могут быть использованы для понимания механизмов, участвующих в развитии ишемического повреждения, что, в свою очередь, может быть использовано при разработке новых терапевтических стратегий. Aim. Stroke is one of the most common causes of disability and mortality worldwide. Multiple experimental models of stroke have focused on monitoring of platelet apoptosis. However, studies on and detection of platelet apoptosis in rats with ischemic stroke are very scarce. We investigated platelet apoptosis in rats with global brain ischemia using flow cytometry. Methods. Experiments were carried out on healthy, adult Wistar male rats weighing 300-350 g. The rats were divided into the following 2 groups: intact rats and rats with global brain ischemia. Global brain ischemia was induced by two-vessel (2-VO) carotid occlusion in combination with hypotension. Systemic blood pressure was reduced by 40-45 mm Hg by inducing haemorrhage. Platelets were isolated by gel filtration on Sepharose 2B. For evaluation of phosphatidylserine (PS) externalization, platelets were incubated with Annexin V-PE and analyzed on FACSCalibur (BD Biosciences). Mitochondrial membrane potential (DY) was measured during platelets apoptosis using JC-1, a mitochondrial membrane potential indicator. Platelets were analyzed by flow cytometry immediately after the incubation. Results. PS externalization on platelets was significantly greater after global brain ischemia (53.45 ± 4.21%) than in the control group (5.27 ± 2.40%). Pronounced depolarization of mitochondrial membrane potential (DYm) confirmed this finding. In the rat group with experimental brain ischemia, almost 40% (35.24 ± 5.21%) of platelets were depolarized. Conclusion. Our results provide insight into mechanisms involved in platelet apoptosis during ischemic stroke and can be used in further development of new therapeutic strategies.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

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