DOCSLIB.ORG

The Mitochondrial Respiratory Chain Has a Critical Role in the Antiviral

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Mitochondrial Respiratory Chain Has a Critical Role in the Antiviral Laboratory Investigation (2012) 92, 125–134 & 2012 USCAP, Inc All rights reserved 0023-6837/12 $32.00 The mitochondrial respiratory chain has a critical role in the antiviral process in Coxsackievirus B3-induced myocarditis Linda Ebermann1,2, Sylwia Wika1, Inga Klumpe1,2, Elke Hammer3, Karin Klingel4, Dirk Lassner5, Uwe Vo¨lker3, Ulrike Erben6, Heinz Zeichhardt7, Heinz-Peter Schultheiss1 and Andrea Do¨rner1 Well-established differences in Coxsackievirus B3 (CVB3) elimination in resistant C57BL/6 and permissive A.SW/SnJ mice provide suitable models for studying the significance of the link between mitochondrial respiratory chain (RC), antioxidative stress components and mitochondrion-related apoptosis in the context of myocardial virus elimination. Distinct myocardial CVB3 titer in C57BL/6 (2.5±1.4 Â 104 plaque-forming units (p.f.u.)/g tissue) and A.SW/SnJ mice (1.4±0.8 Â 107 p.f.u./g) were associated with differences in the cardiac mitochondrial function 8 days post infection (p.i.). Infected C57BL/6 mouse hearts disclosed increased complex I (CI) and CIII activity, but restricted CII and normal CIV activity of RC. Reduced expression of the antioxidative catalase was accompanied by elevated lipid peroxidation (LPO), indicating oxidative stress. Intrinsic apoptosis was activated demonstrated by elevated levels of Bax, Bcl-2, caspase 3 and DNA degradation. In contrast, all myocardial RC complex activities were restricted in CVB3-infected A.SW/SnJ mice. The antioxidative system provided sufficient protection against oxidative stress shown by an elevated catalase expression and unaltered LPO. Bax and Bcl-2 levels were unchanged in CVB3-infected A.SW/SnJ mice, while caspase 3 was mod- erately increased but no DNA degradation was detectable. Correlation analyses including data from the two mouse strains revealed that reduced CVB3 titer correlated with increased CI and CIII activity, oxidative stress as well as active apoptosis during acute myocarditis (MC). C57BL/6 mice completely eliminated CVB3 and inflammation and normalized all intracellular parameters, while A.SW/SnJ mice showed permanently restricted CI activity in chronic MC 90 days p.i., at which time the replicating virus was no longer detectable but immunological processes were still active. Consequently, the regulation of energy metabolism appears crucial for an effective virus elimination and may be of prognostic and therapeutic significance for patients with virus-induced MC. Laboratory Investigation (2012) 92, 125–134; doi:10.1038/labinvest.2011.145; published online 3 October 2011 KEYWORDS: apoptosis; Coxsackievirus B3; mitochondria; myocarditis; oxidative phosphorylation; oxidative stress Coxsackievirus B3 (CVB3), a member of the enteroviral the immunology of the host is crucial for the course of the Picornaviridae, is one of the best-described infectious agents disease, intracellular processes of the infected heart that de- associated with myocarditis (MC).1 Interestingly, character- termine the differences in the fate of the virus remain elusive. istics of the virus alone do not explain the vast difference in Mitochondria, the center of cellular energy production, clinical outcomes of CVB3-induced MC. Acute inflammatory have been shown to be prominent targets of viral proteins, heart disease is either characterized by rapid virus elimina- suggesting that they have a central role in the host’s cellular tion and recovery or ongoing chronic inflammation asso- defense system.3–5 The mitochondrial respiratory chain (RC), ciated with virus persistence frequently resulting in dilated the antioxidative system and members of the Bcl-2 cardiomyopathy.2 Although it is widely acknowledged that family strongly influence the mitochondrial integrity and 1Department of Cardiology and Pneumonology, Charite´—Campus Benjamin Franklin, Universita¨tsmedizin Berlin, Berlin, Germany; 2Institute of Biochemistry, Freie Universita¨t Berlin, Berlin, Germany; 3Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt Universita¨t, Greifswald, Germany; 4Department of Molecular Pathology, Universita¨tTu¨bingen, Tu¨bingen, Germany; 5Institute for Cardiac Diagnostic and Therapy (IKDT), Berlin, Germany; 6Department of Gastroenterology/Infectiology/Rheumatology, Charite´—Universita¨tsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany and 7Department of Virology, Charite´—Universita¨tsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany Correspondence: Dr A Do¨rner, PhD, Department of Cardiology and Pneumonology, Charite´—Universita¨tsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: [email protected] Received 1 March 2011; revised 5 August 2011; accepted 16 August 2011 www.laboratoryinvestigation.org | Laboratory Investigation | Volume 92 January 2012 125 Mitochondrial function in CVB3 myocarditis L Ebermann et al consequently need to be examined to understand the link graded 0 for no, 1 for low, 2 for medium and 3 for extensive between mitochondrial function and CVB3 within the immune cell infiltrations. Myocardial and cellular CVB3 infected heart. titers were determined by plaque-forming assay as previously The RC, the final step of ATP production, transfers elec- described.12 trons from donor molecules via complexes I to IV (CI–CIV) to the acceptor molecule O2, generating the transmembrane RNA Preparation and Real-Time PCR electrochemical gradient used by the ATP synthase to syn- Total RNA was isolated from myocardium using TRIzol thesize ATP. Imbalance in this tightly coordinated system reagent (Invitrogen, Karlsruhe, Germany), and cDNA was leads to misrouting of electrons and increased generation of generated using standard protocols. Quantitative real-time reactive oxygen species (ROS).6,7 ROS are highly reactive and PCR was performed to quantify mRNA expression of tumor damages proteins, lipids and nucleic acids. Components of necrosis factor a (TNFa), interleukin 1b (IL-1b) and trans- the antioxidative stress system such as mitochondrial super- forming growth factor b-1 (TGFb) using the Mastercycler oxide dismutase (SOD2) and catalase activity neutralize these realplex system (Eppendorf, Hamburg, Germany) and the toxic radicals. Maladjustment in RC and disturbance of respective TaqMan Gene Expression Assays from Applied the antioxidative system result in mitochondrial instability Biosystems (Darmstadt, Germany). Gene expression was and apoptosis.8 In those cases, members of the Bcl-2 family normalized in relation to the endogenous housekeeping gene specifically modulate mitochondrial processes initiating hypoxanthine phosphoribosyltransferase 1 (HPRT1). programmed cell death.9 While Bcl-2 suppresses apoptosis, Bax increases the permeability of the inner mitochondrial Mitochondrion Isolation membrane, induces the release of proapoptotic factors that Heart tissue was disrupted with scissors in 10 volumes activate the caspase cascade, initiating cellular degradation. of isolation buffer containing 300 mM sucrose, 5 mM We hypothesize here that the regulation of mitochondrial 3-(N-morpholino)propanesulfonic acid, 1 mM glycol-bis function has a significant impact on the myocardial virus (2-aminoethylether)-N,N,N’, N’-tetraacetic acid, 1 mg/ml load in CVB3-induced MC. To test this hypothesis, we used bovine serum albumin, protease inhibitor mix diluted 1:100 two mouse strains that have been well described for their (Sigma-Aldrich, Steinheim, Germany) pH 7.4. Tissue was different capacity to eliminate CVB3 from the heart. While homogenized in a glass potter and subsequently centrifuged CVB3-infected C57BL/6 mice rapidly eliminate the virus and at 1000 g for 10 min at 4 1C. The supernatant was centrifuged recover from MC, A.SW/SnJ mice develop chronic MC based at 12 000 g for 30 min for mitochondrion preparation. on virus persistence.10,11 These mouse models closely reflect The mitochondrial pellet was washed in 200 ml isolation the etiopathologies in human CVB3-induced MC. buffer and again centrifuged at 12 000 g for 30 min. The mitochondria were resuspended in 50 ml isolation buffer. The MATERIALS AND METHODS supernatant was centrifuged for the preparation of cytosolic Model of Murine MC proteins at 16 000 g for 1 h. Protein concentration was All animal studies were performed according to national determined by the bicinchoninic acid test (Pierce, Bonn, guidelines and were approved by the institutional animal care Germany). committee. The investigation conforms to the ‘Guide for the Care and Use of Laboratory Animals’ stated by the US Determination of RC Complex Activities National Institutes of Health. Transfection-derived CVB3 CI activity was measured spectrophotometrically by the (Nancy strain, ATCC VR-30) was propagated on HeLa cells, oxidation of NADH with decylubiquinone at 340 nm, CII isolated and stored at À80 1C until use. Sixteen 6-week-old activity by the oxidation of succinate with ubiquinone at male C57BL/6 mice and 16 age-matched mice of the A.SW/ 600 nm, CIII by the reduction of cytochrome c with SnJ background were intraperitoneally inoculated with decylubiquinol at 550 nm and CIV by the oxidation of 5 Â 105 plaque-forming units (p.f.u.) of CVB3 in 200 mlof reduced cytochrome c at 550 nm, as described in Jarreta et al.13 phosphate-buffered saline (PBS). A subgroup of age-matched C57BL/6 and A.SW/SnJ mice sham-infected with 200 ml PBS Mass-Spectrometry Analyses served as controls. Eight infected and uninfected mice of each Mitochondrial proteins of individual mice (n ¼ 4 per group) strain were
Load more

Recommended publications
  • Establishing the Pathogenicity of Novel Mitochondrial DNA Sequence Variations: a Cell and Molecular Biology Approach
    Mafalda Rita Avó Bacalhau Establishing the Pathogenicity of Novel Mitochondrial DNA Sequence Variations: a Cell and Molecular Biology Approach Tese de doutoramento do Programa de Doutoramento em Ciências da Saúde, ramo de Ciências Biomédicas, orientada pela Professora Doutora Maria Manuela Monteiro Grazina e co-orientada pelo Professor Doutor Henrique Manuel Paixão dos Santos Girão e pela Professora Doutora Lee-Jun C. Wong e apresentada à Faculdade de Medicina da Universidade de Coimbra Julho 2017 Faculty of Medicine Establishing the pathogenicity of novel mitochondrial DNA sequence variations: a cell and molecular biology approach Mafalda Rita Avó Bacalhau Tese de doutoramento do programa em Ciências da Saúde, ramo de Ciências Biomédicas, realizada sob a orientação científica da Professora Doutora Maria Manuela Monteiro Grazina; e co-orientação do Professor Doutor Henrique Manuel Paixão dos Santos Girão e da Professora Doutora Lee-Jun C. Wong, apresentada à Faculdade de Medicina da Universidade de Coimbra. Julho, 2017 Copyright© Mafalda Bacalhau e Manuela Grazina, 2017 Esta cópia da tese é fornecida na condição de que quem a consulta reconhece que os direitos de autor são pertença do autor da tese e do orientador científico e que nenhuma citação ou informação obtida a partir dela pode ser publicada sem a referência apropriada e autorização. This copy of the thesis has been supplied on the condition that anyone who consults it recognizes that its copyright belongs to its author and scientific supervisor and that no quotation from the
    [Show full text]
  • The First Cells Were Most Likely Very Simple Prokaryotic Forms. Ra- Spirochetes
    T HE O RIGIN OF E UKARYOTIC C ELLS The first cells were most likely very simple prokaryotic forms. Ra- spirochetes. Ingestion of prokaryotes that resembled present-day diometric dating indicates that the earth is 4 to 5 billion years old cyanobacteria could have led to the endosymbiotic development of and that prokaryotes may have arisen more than 3.5 billion years chloroplasts in plants. ago. Eukaryotes are thought to have first appeared about 1.5 billion Another hypothesis for the evolution of eukaryotic cells proposes years ago. that the prokaryotic cell membrane invaginated (folded inward) to en- The eukaryotic cell might have evolved when a large anaerobic close copies of its genetic material (figure 1b). This invagination re- (living without oxygen) amoeboid prokaryote ingested small aerobic (liv- sulted in the formation of several double-membrane-bound entities ing with oxygen) bacteria and stabilized them instead of digesting them. (organelles) in a single cell. These entities could then have evolved This idea is known as the endosymbiont hypothesis (figure 1a) and into the eukaryotic mitochondrion, nucleus, and chloroplasts. was first proposed by Lynn Margulis, a biologist at Boston Univer- Although the exact mechanism for the evolution of the eu- sity. (Symbiosis is an intimate association between two organisms karyotic cell will never be known with certainty, the emergence of of different species.) According to this hypothesis, the aerobic bac- the eukaryotic cell led to a dramatic increase in the complexity and teria developed into mitochondria, which are the sites of aerobic diversity of life-forms on the earth. At first, these newly formed eu- respiration and most energy conversion in eukaryotic cells.
    [Show full text]
  • Selective Induction of Apoptosis in HIV-Infected Macrophages
    Selective Induction of Apoptosis in HIV-infected Macrophages by Simon Xin Min Dong A thesis submitted in partial fulfillment of the requirements for the Doctorate in Philosophy degree in Microbiology and Immunology Department of Biochemistry, Microbiology, and Immunology Faculty of Medicine University of Ottawa © Simon Xin Min Dong, Ottawa, Canada, 2020 Abstract The eradication of Human Immunodeficiency Virus (HIV) from infected patients is one of the major medical problems of our time, primarily due to HIV reservoir formation. Macrophages play important roles in HIV reservoir formation: once infected, they shield HIV against host anti-viral immune responses and anti-retroviral therapies, help viral spread and establish infection in anatomically protected sites. Thus, it is imperative to selectively induce the apoptosis of HIV-infected macrophages for a complete cure of this disease. I hypothesize that HIV infection dysregulates the expression of some specific genes, which is essential to the survival of infected host cells, and these genes can be targeted to selectively induce the apoptosis of HIV-infected macrophages. My objective is to identify the genes that can be targeted to eradicate HIV reservoir in macrophages, and to briefly elucidate the mechanism of cell death induced by targeting one of the identified genes. A four-step strategy was proposed to reach the goal. First, 90k shRNA lentivirus pool technology and microarray analysis were employed in a genome-wide screen of genes and 28 promising genes were found. Second, siRNA silencing was applied to validate these genes with 2 different HIV-1 viruses; as a result, 4 genes, Cox7a2, Znf484, Cdk2, and Cstf2t, were identified to be novel gene targets.
    [Show full text]
  • Bioenergetics and Metabolism Mitochondria Chloroplasts
    Bioenergetics and metabolism Mitochondria Chloroplasts Peroxisomes B. Balen Chemiosmosis common pathway of mitochondria, chloroplasts and prokaryotes to harness energy for biological purposes → chemiosmotic coupling – ATP synthesis (chemi) + membrane transport (osmosis) Prokaryotes – plasma membrane → ATP production Eukaryotes – plasma membrane → transport processes – membranes of cell compartments – energy-converting organelles → production of ATP • Mitochondria – fungi, animals, plants • Plastids (chloroplasts) – plants The essential requirements for chemiosmosis source of high-energy e- membrane with embedded proton pump and ATP synthase energy from sunlight or the pump harnesses the energy of e- transfer to pump H+→ oxidation of foodstuffs is proton gradient across the membrane used to create H+ gradient + across a membrane H gradient serves as an energy store that can be used to drive ATP synthesis Figures 14-1; 14-2 Molecular Biology of the Cell (© Garland Science 2008) Electron transport processes (A) mitochondrion converts energy from chemical fuels (B) chloroplast converts energy from sunlight → electron-motive force generated by the 2 photosystems enables the chloroplast to drive electron transfer from H2O to carbohydrate → chloroplast electron transfer is opposite of electron transfer in a mitochondrion Figure 14-3 Molecular Biology of the Cell (© Garland Science 2008) Carbohydrate molecules and O2 are products of the chloroplast and inputs for the mitochondrion Figure 2-41; 2-76 Molecular Biology of the Cell (© Garland
    [Show full text]
  • Multi-Targeted Mechanisms Underlying the Endothelial Protective Effects of the Diabetic-Safe Sweetener Erythritol
    Multi-Targeted Mechanisms Underlying the Endothelial Protective Effects of the Diabetic-Safe Sweetener Erythritol Danie¨lle M. P. H. J. Boesten1*., Alvin Berger2.¤, Peter de Cock3, Hua Dong4, Bruce D. Hammock4, Gertjan J. M. den Hartog1, Aalt Bast1 1 Department of Toxicology, Maastricht University, Maastricht, The Netherlands, 2 Global Food Research, Cargill, Wayzata, Minnesota, United States of America, 3 Cargill RandD Center Europe, Vilvoorde, Belgium, 4 Department of Entomology and UCD Comprehensive Cancer Center, University of California Davis, Davis, California, United States of America Abstract Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM) and high glucose (30 mM) or diabetic stressors (e.g. SIN-1) using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions) has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite). Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets.
    [Show full text]
  • Origin and Evolution of Plastids and Mitochondria : the Phylogenetic Diversity of Algae
    Cah. Biol. Mar. (2001) 42 : 11-24 Origin and evolution of plastids and mitochondria : the phylogenetic diversity of algae Catherine BOYEN*, Marie-Pierre OUDOT and Susan LOISEAUX-DE GOER UMR 1931 CNRS-Goëmar, Station Biologique CNRS-INSU-Université Paris 6, Place Georges-Teissier, BP 74, F29682 Roscoff Cedex, France. *corresponding author Fax: 33 2 98 29 23 24 ; E-mail: [email protected] Abstract: This review presents an account of the current knowledge concerning the endosymbiotic origin of plastids and mitochondria. The importance of algae as providing a large reservoir of diversified evolutionary models is emphasized. Several reviews describing the plastidial and mitochondrial genome organization and gene content have been published recently. Therefore we provide a survey of the different approaches that are used to investigate the evolution of organellar genomes since the endosymbiotic events. The importance of integrating population genetics concepts to understand better the global evolution of the cytoplasmically inherited organelles is especially emphasized. Résumé : Cette revue fait le point des connaissances actuelles concernant l’origine endosymbiotique des plastes et des mito- chondries en insistant plus particulièrement sur les données portant sur les algues. Ces organismes représentent en effet des lignées eucaryotiques indépendantes très diverses, et constituent ainsi un abondant réservoir de modèles évolutifs. L’organisation et le contenu en gènes des génomes plastidiaux et mitochondriaux chez les eucaryotes ont été détaillés exhaustivement dans plusieurs revues récentes. Nous présentons donc une synthèse des différentes approches utilisées pour comprendre l’évolution de ces génomes organitiques depuis l’événement endosymbiotique. En particulier nous soulignons l’importance des concepts de la génétique des populations pour mieux comprendre l’évolution des génomes à transmission cytoplasmique dans la cellule eucaryote.
    [Show full text]
  • Screening and Identification of Hub Genes in Bladder Cancer by Bioinformatics Analysis and KIF11 Is a Potential Prognostic Biomarker
    ONCOLOGY LETTERS 21: 205, 2021 Screening and identification of hub genes in bladder cancer by bioinformatics analysis and KIF11 is a potential prognostic biomarker XIAO‑CONG MO1,2*, ZI‑TONG ZHANG1,3*, MENG‑JIA SONG1,2, ZI‑QI ZHOU1,2, JIAN‑XIONG ZENG1,2, YU‑FEI DU1,2, FENG‑ZE SUN1,2, JIE‑YING YANG1,2, JUN‑YI HE1,2, YUE HUANG1,2, JIAN‑CHUAN XIA1,2 and DE‑SHENG WENG1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine; 2Department of Biotherapy, Sun Yat‑Sen University Cancer Center; 3Department of Radiation Oncology, Sun Yat‑Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China Received July 31, 2020; Accepted December 18, 2020 DOI: 10.3892/ol.2021.12466 Abstract. Bladder cancer (BC) is the ninth most common immunohistochemistry and western blotting. In summary, lethal malignancy worldwide. Great efforts have been devoted KIF11 was significantly upregulated in BC and might act as to clarify the pathogenesis of BC, but the underlying molecular a potential prognostic biomarker. The present identification mechanisms remain unclear. To screen for the genes associated of DEGs and hub genes in BC may provide novel insight for with the progression and carcinogenesis of BC, three datasets investigating the molecular mechanisms of BC. were obtained from the Gene Expression Omnibus. A total of 37 tumor and 16 non‑cancerous samples were analyzed to Introduction identify differentially expressed genes (DEGs). Subsequently, 141 genes were identified, including 55 upregulated and Bladder cancer (BC) is the ninth most common malignancy 86 downregulated genes. The protein‑protein interaction worldwide with substantial morbidity and mortality.
    [Show full text]
  • Localization of the Mitochondrial Ftsz Protein in a Dividing Mitochondrion Mitochondria Are Ubiquitous Organelles That Play Crit
    C2001 The Japan Mendel Society Cytologia 66: 421-425, 2001 Localization of the Mitochondrial FtsZ Protein in a Dividing Mitochondrion Manabu Takahara*, Haruko Kuroiwa, Shin-ya Miyagishima, Toshiyuki Mori and Tsuneyoshi Kuroiwa Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113-0033, Japan Accepted November 2, 2001 Summary FtsZ protein is essential for bacterial cell division, and is also involved in plastid and mitochondrial division. However, little is known of the function of FtsZ in the mitochondrial division process. Here, using electron microscopy, we revealed that the mitochondrial FtsZ (CmFtsZ 1) local- izes at the constricted isthmus of a dividing mitochondrion on the inner (matrix-side) surface of the mitochondrion. These results strongly suggest that the mitochondrial FtsZ acts as a ring structure on the inner surface of mitochondria. Key words Cyanidionschyzon merolae, FtsZ, FtsZ ring, mitochondria, mitochondrion-dividing ring (MD ring) . Mitochondria are ubiquitous organelles that play critical roles in respiration and ATP synthesis in almost all eukaryotic cells. Mitochondria are thought to have originated from a-proteobacteria through an endosymbiont event. Like bacteria, they multiply by the binary fission of pre-existing mitochondria. Although the role of mitochondria in respiration and ATP production is well under- stood, little is known about the proliferation of mitochondria in cells. In plastids, which also arose from prokaryotic endosymbionts, the ring structure that appears at the constricted isthmus of a dividing plastid (the plastid-dividing ring or PD ring) has been iden- tified as the plastid division apparatus (Mita et al. 1986). The PD ring is widespread among plants and algae, and consists of an outer (cytosolic) ring and an inner (stromal) ring in most species.
    [Show full text]
  • A True Symbiosis for the Mitochondria Evolution
    : O tics pe ge n r A e c n c e e o s i s B Morelli et al, Bioenergetics 2016, 5:2 Bioenergetics: Open Access DOI: 10.4172/2167-7662.1000137 ISSN: 2167-7662 Letter to Editor Open Access A True Symbiosis for the Mitochondria Evolution Alessandro Morelli1* and Camillo Rosano2 1University of Genova, School of Medical and Pharmaceutical Sciences, Department of Pharmacy, Biochemistry Laboratory, Italy 2UO Proteomics, IRCCS AOU San Martino, IST National Institute for Cancer Research, Largo Rosanna Benzi, Genova, Italy *Corresponding author: Alessandro Morelli, University of Genova, School of Medical and Pharmaceutical Sciences, Department of Pharmacy, Biochemistry Laboratory, Italy, Tel: +39 010 3538153; E-mail: [email protected] Rec Date: June 10, 2016; Acc Date: June 22, 2016; Pub Date: June 24, 2016 Copyright: © 2016 Morelli A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Citation: Morelli A, Rosano C (2016) A True Symbiosis for the Mitochondria Evolution. Bioenergetics 5: 228. doi:10.4172/2167-7662.1000137 Introduction assimilated within eukaryotic cells much later than what initially thought [10]. Endosymbiotic theory (or Symbiogenesis) is an evolutionary theory that was initially proposed more than 100 years ago [1] to explain the These revolutionary data together with the hypothesis by our and origins of eukaryotic cells from the prokaryotic ones. This theory others groups about the possible existence of “extra-mitochondrial” postulated that several key organelles of eukaryotes could have been structures in Eukaryotes with OXPHOS and ATP synthesis perfectly originated as a symbiosis between separate organisms.
    [Show full text]
  • Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
    Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement.
    [Show full text]
  • Mitoxplorer, a Visual Data Mining Platform To
    mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, Cecilia Garcia-Perez, José Villaveces, Salma Gamal, Giovanni Cardone, Fabiana Perocchi, et al. To cite this version: Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, et al.. mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dy- namics and mutations. Nucleic Acids Research, Oxford University Press, 2020, 10.1093/nar/gkz1128. hal-02394433 HAL Id: hal-02394433 https://hal-amu.archives-ouvertes.fr/hal-02394433 Submitted on 4 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Nucleic Acids Research, 2019 1 doi: 10.1093/nar/gkz1128 Downloaded from https://academic.oup.com/nar/advance-article-abstract/doi/10.1093/nar/gkz1128/5651332 by Bibliothèque de l'université la Méditerranée user on 04 December 2019 mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim1,†, Prasanna Koti1,†, Adrien Bonnard2, Fabio Marchiano3, Milena Durrbaum¨ 1, Cecilia Garcia-Perez4, Jose Villaveces1, Salma Gamal1, Giovanni Cardone1, Fabiana Perocchi4, Zuzana Storchova1,5 and Bianca H.
    [Show full text]
  • Electron Transport Discovery Four Complexes Complex I: Nadhà Coqh2
    BI/CH 422/622 OUTLINE: Pyruvate pyruvate dehydrogenase Krebs’ Cycle How did he figure it out? Overview 8 Steps Citrate Synthase Aconitase Isocitrate dehydrogenase Ketoglutarate dehydrogenase Succinyl-CoA synthetase Succinate dehydrogenase Fumarase Malate dehydrogenase Energetics Regulation Summary Oxidative Phosphorylation Energetics (–0.16 V needed for making ATP) Mitochondria Transport (2.4 kcal/mol needed to transport H+ out) Electron transport Discovery Four Complexes Complex I: NADHà CoQH2 Complex II: Succinateà CoQH2 2+ Complex III: CoQH2à Cytochrome C (Fe ) 2+ Complex IV: Cytochrome C (Fe ) à H2O Electron Transport à O2 Inhibitors of Electron Transport Big Drop! • Inhibitors all stop ET and ATP synthesis: very toxic! Spectral work Big Drop! NADH Cyto-a3 Cyto-c1 Big Drop! Cyto-b Cyto-c Cyto-a Fully reduced Flavin Cyto-c + rotenone + antimycin A 300 350 400 450 500 550 600 650 700 1 Electron Transport Electron-Transport Chain Complexes Contain a Series of Electron Carriers • Better techniques for isolating and handling mitochondria, and isolated various fractions of the inner mitochondrial membrane • Measure E°’ • They corresponded to these large drops, and they contained the redox compounds isolated previously. • When assayed for what reactions they could perform, they could perform certain redox reactions and not others. • When isolated, including isolating the individual redox compounds, and measuring the E°’ for each, it was clear that an electron chain was occurring; like a wire! • Lastly, when certain inhibitors were added, some of the redox reactions could be inhibited and others not. Site of the inhibition could be mapped. Electron Transport Electron-Transport Chain Complexes Contain a Series of Electron Carriers • Better techniques for isolating and handling mitochondria, and isolated various fractions of the inner mitochondrial membrane • Measure E°’ • They corresponded to these large drops, and they contained the redox compounds isolated previously.
    [Show full text]