Literatura académica sobre el tema "Mitochondria fusion"
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Artículos de revistas sobre el tema "Mitochondria fusion":
1
Murata, Daisuke, Kenta Arai, Miho Iijima y Hiromi Sesaki. "Mitochondrial division, fusion and degradation". Journal of Biochemistry 167, n.º 3 (4 de diciembre de 2019): 233–41. http://dx.doi.org/10.1093/jb/mvz106.
Resumen
Abstract The mitochondrion is an essential organelle for a wide range of cellular processes, including energy production, metabolism, signal transduction and cell death. To execute these functions, mitochondria regulate their size, number, morphology and distribution in cells via mitochondrial division and fusion. In addition, mitochondrial division and fusion control the autophagic degradation of dysfunctional mitochondria to maintain a healthy population. Defects in these dynamic membrane processes are linked to many human diseases that include metabolic syndrome, myopathy and neurodegenerative disorders. In the last several years, our fundamental understanding of mitochondrial fusion, division and degradation has been significantly advanced by high resolution structural analyses, protein-lipid biochemistry, super resolution microscopy and in vivo analyses using animal models. Here, we summarize and discuss this exciting recent progress in the mechanism and function of mitochondrial division and fusion.
2
Seo, Young Ah, Veronica Lopez y Shannon L. Kelleher. "A histidine-rich motif mediates mitochondrial localization of ZnT2 to modulate mitochondrial function". American Journal of Physiology-Cell Physiology 300, n.º 6 (junio de 2011): C1479—C1489. http://dx.doi.org/10.1152/ajpcell.00420.2010.
Resumen
Female reproductive tissues such as mammary glands, ovaries, uterus, and placenta are phenotypically dynamic, requiring tight integration of bioenergetic and apoptotic mechanisms. Mitochondrial zinc (Zn) pools have emerged as a central player in regulating bioenergetics and apoptosis. Zn must first be imported into mitochondria to modulate mitochondrion-specific functions; however, mitochondrial Zn import mechanisms have not been identified. Here we documented that the Zn transporter ZnT2 is associated with the inner mitochondrial membrane and acts as an auxiliary Zn importer into mitochondria in mammary cells. We found that attenuation of ZnT2 expression significantly reduced mitochondrial Zn uptake and total mitochondrial Zn pools. Moreover, expression of a ZnT2-hemagglutinin (HA) fusion protein was localized to mitochondria and significantly increased Zn uptake and mitochondrial Zn pools, directly implicating ZnT2 in Zn import into mitochondria. Confocal microscopy of truncated and point mutants of ZnT2-green fluorescent protein (GFP) fusion proteins revealed a histidine-rich motif (51HH XH54) in the NH2 terminus that is important for mitochondrial targeting of ZnT2. More importantly, the expansion of mitochondrial Zn pools by ZnT2 overexpression significantly reduced ATP biogenesis and mitochondrial oxidation concurrent with increased apoptosis, suggesting a functional role for ZnT2-mediated Zn import into mitochondria. These results identify the first Zn transporter directly associated with mitochondria and suggest that unique secretory tissues such as the mammary gland require novel mechanisms to modulate mitochondrion-specific functions.
3
Twig, Gilad, Xingguo Liu, Marc Liesa, Jakob D. Wikstrom, Anthony J. A. Molina, Guy Las, Gal Yaniv, György Hajnóczky y Orian S. Shirihai. "Biophysical properties of mitochondrial fusion events in pancreatic β-cells and cardiac cells unravel potential control mechanisms of its selectivity". American Journal of Physiology-Cell Physiology 299, n.º 2 (agosto de 2010): C477—C487. http://dx.doi.org/10.1152/ajpcell.00427.2009.
Resumen
Studies in various types of cells find that, on average, each mitochondrion becomes involved in a fusion event every 15 min, depending on the cell type. As most contact events do not result in mitochondrial fusion, it is expected that properties of the individual mitochondrion determine the likelihood of a fusion event. However, apart from membrane potential, the properties that influence the likelihood of entering a fusion event are not known. Here, we tag and track individual mitochondria in H9c2, INS1, and primary β-cells and determine the biophysical properties that increase the likelihood of a fusion event. We found that the probability for fusion is independent of contact duration and organelle dimensions, but it is influenced by organelle motility. Furthermore, the history of a previous fusion event of the individual mitochondrion influenced both the likelihood for a subsequent fusion event, as well as the site on the mitochondrion at which the fusion occurred. These observations unravel the specific properties that distinguish mitochondria that will enter fusion events from the ones that will not. Altogether, these properties may help to elucidate the molecular mechanisms that regulate fusion at the level of the single mitochondrion.
4
Haseeb, Abdul, Hong Chen, Yufei Huang, Ping Yang, Xuejing Sun, Adeela Iqbal, Nisar Ahmed et al. "Remodelling of mitochondria during spermiogenesis of Chinese soft-shelled turtle (Pelodiscus sinensis)". Reproduction, Fertility and Development 30, n.º 11 (2018): 1514. http://dx.doi.org/10.1071/rd18010.
Resumen
Mitochondria are vital cellular organelles that have the ability to change their shape under different conditions, such as in response to stress, disease, changes in metabolic rate, energy requirements and apoptosis. In the present study, we observed remodelling of mitochondria during spermiogenesis and its relationship with mitochondria-associated granules (MAG). At the beginning of spermiogenesis, mitochondria are characterised by their round shape. As spermiogenesis progresses, the round-shaped mitochondria change into elongated and then swollen mitochondria, subsequently forming a crescent-like shape and finally developing into onion-like shaped mitochondria. We also noted changes in mitochondrial size, location and patterns of cristae at different stages of spermiogenesis. Significant differences (P < 0.0001) were found in the size of the different-shaped mitochondria. In early spermatids transitioning to the granular nucleus stage, the size of the mitochondria decreased, but increased subsequently during spermiogenesis. Changes in size and morphological variations were achieved through marked mitochondrial fusion. We also observed a non-membranous structure (MAG) closely associated with mitochondria that may stimulate or control fusion during mitochondrial remodelling. The end product of this sophisticated remodelling process in turtle spermatozoa is an onion-like mitochondrion. The acquisition of this kind of mitochondrial configuration is one strategy for long-term sperm storage in turtles.
5
Higuchi-Sanabria, Ryo, Joseph K. Charalel, Matheus P. Viana, Enrique J. Garcia, Cierra N. Sing, Andrea Koenigsberg, Theresa C. Swayne et al. "Mitochondrial anchorage and fusion contribute to mitochondrial inheritance and quality control in the budding yeast Saccharomyces cerevisiae". Molecular Biology of the Cell 27, n.º 5 (marzo de 2016): 776–87. http://dx.doi.org/10.1091/mbc.e15-07-0455.
Resumen
Higher-functioning mitochondria that are more reduced and have less ROS are anchored in the yeast bud tip by the Dsl1-family protein Mmr1p. Here we report a role for mitochondrial fusion in bud-tip anchorage of mitochondria. Fluorescence loss in photobleaching (FLIP) and network analysis experiments revealed that mitochondria in large buds are a continuous reticulum that is physically distinct from mitochondria in mother cells. FLIP studies also showed that mitochondria that enter the bud can fuse with mitochondria that are anchored in the bud tip. In addition, loss of fusion and mitochondrial DNA (mtDNA) by deletion of mitochondrial outer or inner membrane fusion proteins (Fzo1p or Mgm1p) leads to decreased accumulation of mitochondria at the bud tip and inheritance of fitter mitochondria by buds compared with cells with no mtDNA. Conversely, increasing the accumulation and anchorage of mitochondria in the bud tip by overexpression of MMR1 results in inheritance of less-fit mitochondria by buds and decreased replicative lifespan and healthspan. Thus quantity and quality of mitochondrial inheritance are ensured by two opposing processes: bud-tip anchorage by mitochondrial fusion and Mmr1p, which favors bulk inheritance; and quality control mechanisms that promote segregation of fitter mitochondria to the bud.
6
Zheng, Yunsi, Anqi Luo y Xiaoquan Liu. "The Imbalance of Mitochondrial Fusion/Fission Drives High-Glucose-Induced Vascular Injury". Biomolecules 11, n.º 12 (27 de noviembre de 2021): 1779. http://dx.doi.org/10.3390/biom11121779.
Resumen
Emerging evidence shows that mitochondria fusion/fission imbalance is related to the occurrence of hyperglycemia-induced vascular injury. To study the temporal dynamics of mitochondrial fusion and fission, we observed the alteration of mitochondrial fusion/fission proteins in a set of different high-glucose exposure durations, especially in the early stage of hyperglycemia. The in vitro results show that persistent cellular apoptosis and endothelial dysfunction can be induced rapidly within 12 hours’ high-glucose pre-incubation. Our results show that mitochondria maintain normal morphology and function within 4 hours’ high-glucose pre-incubation; with the extended high-glucose exposure, there is a transition to progressive fragmentation; once severe mitochondria fusion/fission imbalance occurs, persistent cellular apoptosis will develop. In vitro and in vivo results consistently suggest that mitochondrial fusion/fission homeostasis alterations trigger high-glucose-induced vascular injury. As the guardian of mitochondria, AMPK is suppressed in response to hyperglycemia, resulting in imbalanced mitochondrial fusion/fission, which can be reversed by AMPK stimulation. Our results suggest that mitochondrial fusion/fission’s staged homeostasis may be a predictive factor of diabetic cardiovascular complications.
7
Knorre, Dmitry A., Konstantin Y. Popadin, Svyatoslav S. Sokolov y Fedor F. Severin. "Roles of Mitochondrial Dynamics under Stressful and Normal Conditions in Yeast Cells". Oxidative Medicine and Cellular Longevity 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/139491.
Resumen
Eukaryotic cells contain dynamic mitochondrial filaments: they fuse and divide. Here we summarize data on the protein machinery driving mitochondrial dynamics in yeast and also discuss the factors that affect the fusion-fission balance. Fission is a general stress response of cells, and in the case of yeast this response appears to be prosurvival. At the same time, even under normal conditions yeast mitochondria undergo continuous cycles of fusion and fission. This seems to be a futile cycle and also expensive from the energy point of view. Why does it exist? Benefits might be the same as in the case of sexual reproduction. Indeed, mixing and separating of mitochondrial content allows mitochondrial DNA to segregate and recombine randomly, leading to high variation in the numbers of mutations per individual mitochondrion. This opens a possibility for effective purifying selection-elimination of mitochondria highly contaminated by deleterious mutations. The beneficial action presumes a mechanism for removal of defective mitochondria. We argue that selective mitochondrial autophagy or asymmetrical distribution of mitochondria during cell division could be at the core of such mechanism.
8
Keng, T., E. Alani y L. Guarente. "The nine amino-terminal residues of delta-aminolevulinate synthase direct beta-galactosidase into the mitochondrial matrix". Molecular and Cellular Biology 6, n.º 2 (febrero de 1986): 355–64. http://dx.doi.org/10.1128/mcb.6.2.355-364.1986.
Resumen
delta-Aminolevulinate synthase, the first enzyme in the heme biosynthetic pathway, is encoded by the nuclear gene HEM1. The enzyme is synthesized as a precursor in the cytoplasm and imported into the matrix of the mitochondria, where it is processed to its mature form. Fusions of beta-galactosidase to various lengths of amino-terminal fragments of delta-aminolevulinate synthase were constructed and transformed into yeast cells. The subcellular location of the fusion proteins was determined by organelle fractionation. Fusion proteins were found to be associated with the mitochondria. Protease protection experiments involving the use of intact mitochondria or mitoplasts localized the fusion proteins to the mitochondrial matrix. This observation was confirmed by fractionation of the mitochondrial compartments and specific activity measurements of beta-galactosidase activity. The shortest fusion protein contains nine amino acid residues of delta-aminolevulinate synthase, indicating that nine amino-terminal residues are sufficient to localize beta-galactosidase to the mitochondrial matrix. The amino acid sequence deduced from the DNA sequence of HEM1 showed that the amino-terminal region of delta-aminolevulinate synthase was largely hydrophobic, with a few basic residues interspersed.
9
Keng, T., E. Alani y L. Guarente. "The nine amino-terminal residues of delta-aminolevulinate synthase direct beta-galactosidase into the mitochondrial matrix." Molecular and Cellular Biology 6, n.º 2 (febrero de 1986): 355–64. http://dx.doi.org/10.1128/mcb.6.2.355.
Resumen
delta-Aminolevulinate synthase, the first enzyme in the heme biosynthetic pathway, is encoded by the nuclear gene HEM1. The enzyme is synthesized as a precursor in the cytoplasm and imported into the matrix of the mitochondria, where it is processed to its mature form. Fusions of beta-galactosidase to various lengths of amino-terminal fragments of delta-aminolevulinate synthase were constructed and transformed into yeast cells. The subcellular location of the fusion proteins was determined by organelle fractionation. Fusion proteins were found to be associated with the mitochondria. Protease protection experiments involving the use of intact mitochondria or mitoplasts localized the fusion proteins to the mitochondrial matrix. This observation was confirmed by fractionation of the mitochondrial compartments and specific activity measurements of beta-galactosidase activity. The shortest fusion protein contains nine amino acid residues of delta-aminolevulinate synthase, indicating that nine amino-terminal residues are sufficient to localize beta-galactosidase to the mitochondrial matrix. The amino acid sequence deduced from the DNA sequence of HEM1 showed that the amino-terminal region of delta-aminolevulinate synthase was largely hydrophobic, with a few basic residues interspersed.
10
Eisner, Verónica, Guy Lenaers y György Hajnóczky. "Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling". Journal of Cell Biology 205, n.º 2 (21 de abril de 2014): 179–95. http://dx.doi.org/10.1083/jcb.201312066.
Resumen
Genetic targeting experiments indicate a fundamental role for mitochondrial fusion proteins in mammalian physiology. However, owing to the multiple functions of fusion proteins, their related phenotypes are not necessarily caused by altered mitochondrial fusion. Perhaps the biggest mystery is presented by skeletal muscle, where mostly globular-shaped mitochondria are densely packed into the narrow intermyofilamental space, limiting the interorganellar interactions. We show here that mitochondria form local networks and regularly undergo fusion events to share matrix content in skeletal muscle fibers. However, fusion events are less frequent and more stable in the fibers than in nondifferentiated myoblasts. Complementation among muscle mitochondria was suppressed by both in vivo genetic perturbations and chronic alcohol consumption that cause myopathy. An Mfn1-dependent pathway is revealed whereby fusion inhibition weakens the metabolic reserve of mitochondria to cause dysregulation of calcium oscillations during prolonged stimulation. Thus, fusion dynamically connects skeletal muscle mitochondria and its prolonged loss jeopardizes bioenergetics and excitation–contraction coupling, providing a potential pathomechanism contributing to myopathies.
Tesis sobre el tema "Mitochondria fusion":
1
Heller, Anne Sabine [Verfasser] y Achim [Akademischer Betreuer] Göpferich. "Targeting mitochondria by mitochondrial fusion, mitochondria-specific peptides and nanotechnology / Anne Sabine Heller. Betreuer: Achim Göpferich". Regensburg : Universitätsbibliothek Regensburg, 2013. http://d-nb.info/103321664X/34.
2
Macchi, Marc. "Contribution à l' étude de la morphogénèse des mitochondries chez la drosophile". Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4051/document.
Resumen
Les mitochondries sont des organelles de quelques micromètres qui proviendraient de l'incorporation d'une alpha-protéobactérie dans le cytoplasme des cellules eucaryotes par endosymbiose. Dans les cellules eucaryotes, la mitochondrie joue un rôle central dans la production d'ATP, mais aussi dans la mort cellulaire programmée par apoptose ainsi que dans la biosynthèse de nombreuses molécules. Les mitochondries sont très polymorphes, leurs taille, forme et organisation varient considérablement selon le type cellulaire ou l'état physiologique ou pathologique de la cellule. Depuis une vingtaine d'année, l'étude des mécanismes qui contrôlent la morphogenèse, la dynamique de fission et de fusion mitochondriale et leurs rôles physiologiques est devenue un domaine majeur dans la recherche sur la mitochondrie. De plus, avec les progrès de la vidéo-microscopie, il est devenu possible de filmer des mitochondries dans le cytoplasme de cellules vivantes. Durant ma thèse, j'ai participé à la caractérisation de la fonction du gène Pantagruelian Mitochondria I (PMI), un nouveau déterminant de la morphologie des mitochondries que nous avons découvert chez la drosophile. PMI est une protéine de la membrane interne qui, en intervenant dans l'organisation de cette membrane, est indispensable à la formation de mitochondries de forme tubulaire. J'ai également contribué au développement d'outils et de méthodologies permettant la visualisation et l'étude de la dynamique mitochondriale dans des embryons de drosophiles vivantsMitochondria are organelles which are a few micrometers long and are originated from the incorporation of an alpha-proteobacteria in the cytoplasm of eukaryotic cells through endosymbiosis. In eukaryotic cells, mitochondria play a central role in ATP production as well as in programmed cell death and in the biosynthesis of many molecules. Mitochondria are highly polymorphic in size and form. Their organization also varies considerably according to the cell type or physiological or pathological state of the cell. In the last two decades, the study of the mechanisms controlling morphogenesis, dynamic of mitochondrial fission and fusion and their physiological roles has become a major research field of mitochondria. In addition, the progress in video-microscopy enable to record mitochondrial dynamics in the cytoplasm of living cells. I participated in the research on the characterization of gene function called Pantagruelian Mitochondria I (PMI), a novel determinant of the mitochondrial morphology that we discovered in Drosophila. PMI, a protein of the inner membrane, is involved in its membrane organization and essential to form tubular mitochondria. I also contributed to the development of experimental tools and protocols to visualize and study the mitochondrial dynamics in living Drosophila embryos. Interestingly, a stereotyped process of mitochondrial remodeling during Drosophila embryogenesis has been found and it raised a question about its role in developmental processes through my work
3
Sauvanet, Cécile. "Caractérisation des acteurs et des mécanismes de la fusion mitochondriale". Thesis, Bordeaux 2, 2011. http://www.theses.fr/2011BOR21883/document.
Resumen
Les mitochondries sont des organites dynamiques qui fusionnent et se divisent continuellement. Cette dynamique est requise pour la biogenèse mitochondriale, la fonction et la dégradation. Les relations entre les OXPHOS, la dynamique et les mécanismes assurant la modulation de la dynamique restent largement inconnus. Nous avons étudié grâce à un essai de fusion in vivo, les relations entre la fusion et les OxPhos dans des cellules de levure portant des mutations ponctuelles dans le gène mitochondrial ATP6 qui sont associés à des maladies chez l’homme. Nous montrons que les défauts des OxPhos provoquent des défauts de fusion de la membrane interne mitochondriale mais pas de la membrane externe. L'inhibition sélective de la fusion de la membrane interne peut être mimée par les ionophores qui dissipent le potentiel de membrane interne, mais pas par des inhibiteurs des phosphorylations oxydatives. Nous montrons une inhibition dominante de fusion qui pourrait être un mécanisme d'exclusion des mitochondries dysfonctionnelles du réseau mitochondrial pour les adresser à la mitophagie. Ces résultats indiquent que les défauts de fusion pourraient contribuer à la pathologie des maladies provoquées par des mutations de l'ADNmt. De plus ces résultats impliquent que dans des cellules, l'inhibition de la fusion dominante pourrait permettre l'exclusion des mitochondries dysfonctionnelles du réseau mitochondrial. La fusion mitochondriale implique de nombreuses protéines de la superfamille des dynamines. Si ces protéines ont été identifiées, les mécanismes moléculaires permettant la fusion restent indéterminés. Dans le but de comprendre ces mécanismes, nous avons choisi de caractériser les protéines Mitofusine 1 et 2, essentielles à la fusion des membranes externes mitochondriales. Ces protéines sont composées de deux domaines coiled-coil et un domaine N-terminal GTPase et des domaines hydrophobes prédits pour être des segments transmembranaires. Après la détermination des activités GTPase des mitofusines, nous avons reconstitué les mitofusines ou des fragments des mitofusines dans des liposomes afin d'étudier leur capacité à fusionner ces liposomes. Les mitofusines, permettent la fusion des liposomes contenant des cardiolipides. Étonnamment, ces événements sont indépendants de la présence du GTP mais nécessitent Mg2+ dans la solution. En utilisant la microscopie électronique, nous montrons que les mitofusines 1 et 2 induisent une déformation des liposomes. Cette capacité permettant de créer localement des régions très courbes (et donc fusogènes) ouvre un nouvel angle pour comprendre les mécanismes moléculaires de la fusion mitochondrialeMitochondria are dynamic organelles that continuously fuse and divide. This dynamic is required for mitochondrial biogenesis, function and degradation. The cross-talk between OXPHOS and dynamics and the mechanisms ensuring modulation of dynamics remain largely unraveled. We have investigated the relationship between fusion and OXPHOS in yeast cells carrying point mutations in the mitochondrial ATP6 gene that are associated to human diseases. We show that OXPHOS defects provoke severe defects of inner membrane, but not outer membrane fusion. Selective inhibition of inner membrane fusion can be recapitulated by ionophores that dissipate the inner membrane potential, but not by inhibitors of OXPHOS. We show a dominant inhibition of fusion that further provides a mechanism for the exclusion of defective mitochondria from the functional mitochondrial network, a pre-requisite for their selective targeting to mitophagy. These results suggest that defects of fusion could contribute to the pathology of diseases caused by mtDNA mutations. Moreover, these results imply that in cells, inhibition of dominant fusion could allow the exclusion of dysfunctional mitochondria mitochondrial network. Mitochondrial fusion involves many proteins of the superfamily of dynamin. If these proteins have been identified, the molecular mechanisms of fusion remain undetermined. In order to understand these mechanisms, we choose to characterize Mitofusin 1 and 2 proteins, essential for outer mitochondrial membrane fusion. These transmembrane proteins are consisting of two coiled-coil domains and one N-terminal GTPase domain. We have characterized GTPase activity of Mitofusin and reconstituted Mitofusins or fragments of Mitofusins into liposomes to study their capacity to fuse these liposomes. Full-length mitofusins can fuse liposomes containing cardiolipins. Surprisingly, these fusion events are independent of GTP but require Mg2+ in the buffer. Using electron microscopy, we show that mitofusin 1 and 2 induce local deformation of liposomes. This capacity of mitofusins to locally create highly curved (and thus fusogenic) membrane regions opens a new angle to understand the molecular mechanisms of mitochondrial fusion
4
Wang, Xinglong. "Impaired Balance of Mitochondria Fission and Fusion in Alzheimer Disease". Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1228318762.
5
De, Vecchis Dario. "Gaining insights into mitochondrial membrane fusion through a structural and dynamic atomistic model of the mitofusin Fzo1p". Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC001.
Resumen
Les mitochondries sont des organites dynamiques dont la morphologie dépend de l’équilibre fusion/fission de leurs membranes. Ce processus essentiel à la survie cellulaire est nommé dynamique mitochondriale et sa dérégulation est associée à des troubles neurologiques. Cependant les mécanismes précis régissant la dynamique mitochondriale ne sont pas élucidés. Cette thèse porte sur la protéine Fzo1p, une grande GTPase de la superfamille des Dynamin-related-Protein. C’est un élément clé impliqué dans la fusion mitochondriale de la membrane externe de la levure. Sa structure et sa dynamique ont été étudiées par modélisation et simulations de dynamiques moléculaires tout-atome dans une bicouche lipidique solvatée. Le modèle structural obtenu tient compte de données expérimentales, de template structuraux, et de modèles ab initio du domaine transmembranaire de Fzo1p. Ce modèle a été validé expérimentalement par mutagenèse dirigée. Des permutations de charges ont confirmé des ponts salins à longue distance prédits dans le modèle. En outre, des mutations ont montré que les domaines coiled-coil de Fzo1p, contrairement à sa partie N-terminale, sont indispensables à sa fonction. L’ensemble des résultats expérimentaux et in silico met en évidence l’implication des domaines charnières dans le changement conformationnel de Fzo1p, ainsi que des résidus critiques affectant sa stabilité. Les précisions atomiques obtenues sur l’interaction de Fzo1p avec le GDP permet de formuler des hypothèses sur le mécanisme moléculaire de la catalyse du GTP pour la fusion membranaire; voire à la compréhension de la dynamique mitochondrialeMitochondria are dynamic organelles whose morphology is determined by fusion and fission of their membranes. This essential process is known as mitochondrial dynamics. Defects in mitochondrial dynamics are associated with neurological disorders making the investigation of physiological relevance. However, the precise sequence of events that lead mitochondrial dynamics are still not well characterised. Fzo1p, a large GTPase of the Dynamin-Related Proteins superfamily, is a key component in mitochondrial outer membrane fusion in yeast. During this PhD project I built a model of the protein Fzo1p. The structure and dynamics of the model was investigated through molecular modelling and all-atom molecular dynamics simulation in a fully hydrated lipid bilayer environment. The Fzo1p structural model integrates information from several template structures, experimental knowledge, as well as ab initio models of the transmembrane segments. The model is validated experimentally through directed mutagenesis, for instance charge-swap mutations confirm predicted long-distance salt bridges. A series of mutants indicate that coiled-coil domains are required for protein function at variance with its N-terminal region. Overall, the experimental and in silico approaches pinpoint the hinge domains involved in the putative conformational change and identifies critical residues affecting protein stability. Finally, key Fzo1p-GDP interactions provide insights about the molecular mechanism of membrane fusion catalysis. The model provides insight on atomic level and proposes a structure that will be instructional to understanding mitochondrial membrane fusion
6
Macchi, Marc. "Contribution à l' étude de la morphogénèse des mitochondries chez la drosophile". Electronic Thesis or Diss., Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4051.
Resumen
Les mitochondries sont des organelles de quelques micromètres qui proviendraient de l'incorporation d'une alpha-protéobactérie dans le cytoplasme des cellules eucaryotes par endosymbiose. Dans les cellules eucaryotes, la mitochondrie joue un rôle central dans la production d'ATP, mais aussi dans la mort cellulaire programmée par apoptose ainsi que dans la biosynthèse de nombreuses molécules. Les mitochondries sont très polymorphes, leurs taille, forme et organisation varient considérablement selon le type cellulaire ou l'état physiologique ou pathologique de la cellule. Depuis une vingtaine d'année, l'étude des mécanismes qui contrôlent la morphogenèse, la dynamique de fission et de fusion mitochondriale et leurs rôles physiologiques est devenue un domaine majeur dans la recherche sur la mitochondrie. De plus, avec les progrès de la vidéo-microscopie, il est devenu possible de filmer des mitochondries dans le cytoplasme de cellules vivantes. Durant ma thèse, j'ai participé à la caractérisation de la fonction du gène Pantagruelian Mitochondria I (PMI), un nouveau déterminant de la morphologie des mitochondries que nous avons découvert chez la drosophile. PMI est une protéine de la membrane interne qui, en intervenant dans l'organisation de cette membrane, est indispensable à la formation de mitochondries de forme tubulaire. J'ai également contribué au développement d'outils et de méthodologies permettant la visualisation et l'étude de la dynamique mitochondriale dans des embryons de drosophiles vivantsMitochondria are organelles which are a few micrometers long and are originated from the incorporation of an alpha-proteobacteria in the cytoplasm of eukaryotic cells through endosymbiosis. In eukaryotic cells, mitochondria play a central role in ATP production as well as in programmed cell death and in the biosynthesis of many molecules. Mitochondria are highly polymorphic in size and form. Their organization also varies considerably according to the cell type or physiological or pathological state of the cell. In the last two decades, the study of the mechanisms controlling morphogenesis, dynamic of mitochondrial fission and fusion and their physiological roles has become a major research field of mitochondria. In addition, the progress in video-microscopy enable to record mitochondrial dynamics in the cytoplasm of living cells. I participated in the research on the characterization of gene function called Pantagruelian Mitochondria I (PMI), a novel determinant of the mitochondrial morphology that we discovered in Drosophila. PMI, a protein of the inner membrane, is involved in its membrane organization and essential to form tubular mitochondria. I also contributed to the development of experimental tools and protocols to visualize and study the mitochondrial dynamics in living Drosophila embryos. Interestingly, a stereotyped process of mitochondrial remodeling during Drosophila embryogenesis has been found and it raised a question about its role in developmental processes through my work
7
Norton, Matthew. "Genome-wide RNAi Screen Identifies Romo1 as a Novel Regulator of Mitochondrial Fusion and Cristae Integrity". Thesis, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23701.
Resumen
Mitochondria exist in a dynamic network regulated by the opposing processes of mitochondrial fusion and fission. Regulation of mitochondrial morphology is critical for metabolism, quality control and cell survival, among other cellular processes. Large GTPases are responsible for shaping the mitochondrial network. Mitofusins 1 and 2 and Opa1 regulate outer and inner mitochondrial membrane fusion, respectively. Conversely, Drp1 is recruited to mitochondria to carry out fission. Although many proteins have been implicated in these processes, there are still many unknowns. We sought to identify novel regulators of mitochondrial morphology and conducted a genome-wide RNAi screen to identify candidate genes. We identified Reactive Oxygen species Modulator 1 (ROMO1) as a novel regulator of mitochondrial fusion and cristae integrity. In the absence of ROMO1, the mitochondrial network fragments and cristae are lost. These defects lead to impaired mitochondrial respiration and sensitization to cytochrome c release and downstream apoptosis. ROMO1 is regulated by mitochondrial REDOX at 4 cysteine residues that couple REDOX signaling to mitochondrial morphology. We have characterized ROMO1 as an interactor with the MINOS complex, required for cristae junction maintenance, and the inner mitochondrial membrane fusion GTPase OPA1. Through these interactions ROMO1 couples cristae junction security to mitochondrial fusion.
8
Nguyen, Phuc Minh Chau. "Fusion Mitochondriale et Effets Vasculaires : rôle de OPA 1 dans l'hypertension artérielle et le vieillissement". Thesis, Angers, 2015. http://www.theses.fr/2015ANGE0073.
Resumen
La morphologie mitochondriale résulte d’un équilibre dynamique entre les processus de fusion et de fission, impactant la physiologie cellulaire. Plusieurs données montrent une relation entre la fonction mitochondriale, des maladies cardiovasculaires et le vieillissement. OPA1 (optic atrophy 1) est une protéine qui contrôle la fusion de la membrane interne de la mitochondrie, et dont la mutation induit la maladie ADOA (autosomal dominant optic atrophy). Les travaux menés récemment indiquent que la mutation OPA1 est impliquée dans le dysfonctionnement cardiaque mais son impact sur la fonction vasculaire est encore inconnu. Notre étude a pour ambition d’examiner le rôle d’OPA1 sur la fonction vasculaire, notamment dans le développement de l’hypertension artérielle et le vieillissement vasculaire. Avec un modèle de souris hétérozygotes Opa1+/-, nous montrons dans cette étude que la protéine OPA1 joue un rôle protecteur dans le système vasculaire. En effet, les souris déficientes en OPA1 développent une hypertension-L-NAME dépendante plus grave qui est associée avec une dysfonction endothéliale plus importante et une altération de remodelage vasculaire. D’autre part, présentant une fonction vasculaire normale à 6 mois, les souris Opa1+/- commencent à développer un dysfonctionnement vasculaire à 12 mois qui pourrait induire le développement de pathologies vasculaires. En conclusion, ces résultats suggèrent pour la première fois que la dynamique mitochondriale peut jouer un rôle important sur la fonction et l’adaptation des vaisseaux dans les conditions pathologiques et dans le vieillissement vasculaire. Des études complémentaires seront nécessaires afin de clarifier le rôle de la protéine OPA1 dans l’hypertension. Ces données peuvent contribuer à la recherche de nouvelles cibles thérapeutiques pour prévenir les complications de l’hypertension et les maladies vasculaires liées à l’âgeDefects in mitochondrial dynamics have been associated with various disorders, including cardiovascular diseases. OPA1 is essential for mitochondrial inner membrane fusion. Mutation in Opa1 is associated with the autosomal dominant optic atrophy (ADOA). Since then, OPA1 has been reported to be associated with cell apoptosis, cell proliferation, mitochondrial ATP synthesis, calcium homeostasis and ROS production. These data suggest that OPA1 has a potential role in vascular cells and subsequently affects vascular function. On the other hand,OPA1 is also associated with age-related changes of mitochondria and simultaneously contribute to the development of many dysfunctions in different organs. In this study, we investigated impacts of OPA1 mutation on vascular function in physiological and pathological condition like hypertension and vascular aging. By using an Opa1+/- heterozygote mouse model, we show that the OPA1 protein plays a protective role in the vascular system. Indeed, Opa1+/- mice developed a hypertension more severe than WT mice which was associated with more important endothelial dysfunction and altered vascular remodeling. In addition, although initial vascular function was normal, at 12 months, Opa1+/- mice displayed vascular dysfunction which might predict onset of vascular diseases at a later time. These results suggest for the first time that mitochondrial dynamics might play an important role in vascular function and adaptation in pathological conditions and in vascular aging. More studies are needed to clarify the role of the protein OPA1 in hypertension. These data may help to identify novel therapeutic targets to prevent complications of hypertension and vascular age-related diseases
9
Frezza, Christian. "OPA1, a mitochondrial pro-fusion protein, regulates the cristae remodelling pathway during apoptosis". Doctoral thesis, Università degli studi di Padova, 2007. http://hdl.handle.net/11577/3426739.
Resumen
Mitochondria are essential organelles for the life of the cells since it is the major source of ATP, key molecule for many endoergonic reaction.
Recently it has been demonstrated that mitochondrial play a key role in many other cellular processes like Ca2+ signaling and programmed cell death.
Following an apoptotic insult mitochondria release cytochrome c and other proteins required in the cytosol for the activation of the effector caspases required for cell demise.
What is remarkable about cytochrome c release is that is fast, complete and usually is not associated with mitochondrial swelling. Thanks to the advances in 3D electron microscopy it has been demonstrated that cristae are not just invagination of the inner mitochondrial membrane (IMM) as previously depicted by Palade (Palade, 1952) but rather distinct compartments of it, separated from the inter membrane space (IMS) by tubular narrow cristae junctions. The majority of cytochrome c and the other respiratory chain components are restricted in this compartment. To reach a complete cytochrome c release in the absence of mitochondrial swelling mitochondria remodel their internal structure: individual cristae fuse and tubular narrow cristae junctions widen; this process, defined cristae remodeling is associated with the mobilization of cytochrome c towards the IMS for its subsequent release across the outer mitochondrial membrane (OMM) (Scorrano et al., 2002). The molecular mechanism beyond this dynamic process is not well understood and in the laboratory where I did my doctoral Thesis it has been hypothesized that OPA1, the only dynamin related protein of the IMM (Alexander et al., 2000; Delettre et al., 2000) could control cristae remodeling. Dynamin related proteins are regulators of mitochondrial morphology promoting mitochondrial fusion and fission. To this family belong Mitofusins (MFN) 1 and 2 in the OMM and OPA1 that resides in the IMM. OPA1 is a large GTPase anchored in the IMM, facing the IMS (Olichon et al., 2002; Satoh et al., 2003); it has been shown that in yeast, its orhologue Mgm1p is required for fusion competent mitochondria by the cooperation with a protein of the same family on the OMM called Fzo1p. In our laboratory it has been demonstrated that in mammalian cells OPA1 promotes mitochondrial fusion through one of the two mammaliam orthologue of Fzo1p called MFN1.
In 2000 two distinct laboratories demonstrated that mutations in OPA1 gene are the cause of dominant optic atrophy (ADOA), the leading case of inherited blindness in human, characterized by selective death of retinal ganglion cell (RGC) (Alexander et al., 2000; Delettre et al., 2000). The fact the mutation in a mitochondrial protein involved in mitochondrial morphology caused cell death opened a new scenario that corroborates the central position of mitochondria in regulating apoptotic signaling.
The aim of my thesis was to analyze the role of OPA1 in mitochondria-dependent apoptosis.
We started with a brute force approach by overexpressing OPA1 in murine embryonic fibroblasts (MEFs) and measuring cells viability in response to intrinsic apoptotic stimuli that specifically trigger apoptosis through the mitochondrial pathway.
Overexpression of wt OPA1 but not of mutant in the GTPase domain (OPA1K301A) or a truncated mutant in the coiled coil domain (OPAR905*) is able to prevent from apoptosis induced by hydrogen peroxide, staurosporine, etoposide and overexpression of tBID, a BH3 only protein of the Bcl-2 family that promotes cristae remodeling. To confirm that OPA1 antiapoptotic activity was exerted at the mitochondrial level we analyzed two aspects of the mitochondrial dysfunction: cytochrome c release and mitochondrial depolarization.
To this aim we overexpressed a mitochondrially targeted red fluorescent protein (mtRFP) as marker of the mitochondrial network and then we immunodecorated cytochrome c with a FITC-conjugated secondary antibody. OPA1 overexpression prevented cytochrome c release in response to intrinsic stimuli while its inactive mutant OPAK301A aggravated cytochrome c release kinetic.
We then analyzed another aspect of the mitochondrial dysfunction: mitochondrial depolarization, taking advantage of the potentiometric probe tetramethylrhodamine-methyl ester (TMRM) which mitochondrial fluorescence is proportional to mitochondrial potential. Overexpression of OPA1, but not of its inactive K301A mutant, prevented mitochondrial depolarization induced by intrinsic stimuli, confirming that OPA may prevent from apoptosis at the mitochondrial level by reducing cytochrome c release and mitochondrial depolarization. How can a dynamin related protein prevent from apoptosis? We asked this because when our study was ongoing an intriguing hypotesys emerged: during apoptosis mitochondrial network undergoes irreversible massive fragmentation; this event and apoptotic cristae remodeling are required for complete cytochrome c release. In principle, OPA1 could prevent apoptosis at both of these levels either counteracting mitochondrial fragmentation thanks to its pro-fusion activity or by the regulation of cristae remodeling. To understand at which of these levels OPA1 was exerting its antiapototic activity, we started a genetic approach, overexpressing OPA1 in Mfn1-/-, where OPA1 pro-fusion activity was prejudiced.
Overexpression of OPA1 in these cells prevented from apoptosis induced by intrinsic stimuli; in view of the fact that a residual pro-fusion activity of OPA1 could be mediated by the presence of MFN2 we repeated the same experiments in cells in which both mitofusins were ablated (DMF). Also in this conditions OPA1 prevented from apoptosis at the mitochondrial level, slowing down cytochrome c release kinetic. OPA1 has an antiapoptotica function that is independent of its pro-fusion activity on the mitochondrial network.
At this point we asked whether OPA1 may have a role on apoptotic cristae remodeling. We generated stable cell lines that stably overexpressed OPA1 and its K301A mutant both in wt and in Mfn1-/- cells and a cell line depleted of OPA1 by short hairpin RNA interference (shOPA1RNAi). We then isolated mitochondria and measured cytochrome c release induced by recombinant caspase 8 cleaved BID (cBID) using a specific ELISA immunoassay. Stable overexpression of OPA1 is able to prevent cytochrome c relase independently of MFN1 while its downregulation dramatically increases its release. Using a specific assay we observed that OPA1 is also able to prevent cytochrome c mobilization from the cristae independently of MFN. These results were confirmed by the fact that overexpression of the OPA1K301A mutant increased cytochrome c mobilization that was almost complete when OPA1 levels were depleted by RNAi. A thorough morphometric analysis of isolated mitochondria from these cell lines, associated with 3D reconstruction of electron microscopy tomography, showed that OPA1 controls cristae morphology and prevents cristae junction widening in response to cBID. To better understand the molecular mechanism through which OPA1 controls cristae remodeling and cristae junctions diameter we based our hypothesis on the possible analogy with vesciculation processes regulated by cytosolic dynamin, where GTPase activity of it mediated mechanoenzimatic constriction of the vesicle collar. Despite this analogy, we should mention that OPA1, unlike dynamin, is located on the inner side of the membrane to be constricted and not on the outside as dynamin complicating the model. First, we analyzed biochemical characteristic of OPA1: gel filtration studies showed that OPA1 is eluted at very high molecular weight fractions (>600 KDa) and in response to cBID incubation it is retrieved in low molecular weight fractions. Parallel studies in our laboratory demonstrated that OPA1 is processed by a rhomboid protease, PARL, into a short form found soluble in the IMS that is responsible for the antiapototic but not of the pro-fusion activity of OPA1. We therefore reasoned that OPA1 could organize into high molecular weight complexes made up at least by the PARL generated soluble form and the membrane bound form of OPA1. To confirm this hypothesis we crosslinked this complex and confirmed the presence of a high molecular weight immunoreactive band for OPA1 that disappear following the mechanical expansion of the cristae induced by osmotic swelling. These crosslinker-stabilized oligomers contain both the soluble and the membrane bound forms of OPA1 as demonstrated by their immunoreactivity for properly tagged and co-expressed forms.
The OPA1-containing oligomers is targeted by cBID in a time dependent manner and OPA1 overexpression stabilizes these complexes. We can conclude that OPA1 controls cytochrome c mobilization and cristae remodeling that occurs during apoptosis. This function of OPA1 is independent of MFNs and is correlated to the formation of high molecular weight complexes.
The data collected so far on OPA1 antiapoptotic function open a new scenario. First we need to investigate on the molecular composition of these complexes in normal and apoptotic conditions. To this aim we started a biochemical study on OPA1-containing complexes in mitochondria isolated from different genetic background in normal and apoptotic conditions. The proteomic analysis of the proteins eventually found in complex with OPA1 will allow us to comprehend the function and regulation of OPA1 oligomers before and after cell death induction.
OPA1 appears as a crucial protein in the apoptotic process; as a confirmation of this, it has been found that OPA1 is highly overexpressed in some lung cancer (Dean Fennel, personal communication); we then asked whether OPA1 could be a target for the development of new drugs that enhance apoptosis in tumor cells. To this aim, we started a collaboration with Stefano Moro from the Department of Medicinal Chemistry of the University of Padova, to generate a library of candidate inhibitors of OPA1 performing a virtual screening of compounds targeted to the GTPase pocket of OPA1 obtained following an homology modeling on the Dyctiostelium Discoideum GTPase domain of Dynamin A.
In conclusion, the data presented in this doctoral thesis show that mitochondrial protein OPA1 participates in the regulation of cytochrome c mobilization and cristae remodeling during apoptosis. We demonstrated that OPA1 organizes into high molecular weight complexes which disruption correlates with cristae junction widening. This function is distinct from its role in mitochondrial morphology and this suggest a bifurcation and specialization of OPA1 function during evolution.
10
Alsayyah, Cynthia. "Régulation de la fusion mitochondriale par le Système Ubiquitine Protéasome et les contacts physiques mitochondrie - peroxysomes chez la levure Saccharomyces cerevisiae". Electronic Thesis or Diss., Université Paris sciences et lettres, 2021. https://theses.hal.science/tel-03810525.
Resumen
Les mitochondries sont des organelles très dynamiques qui subissent des phénomènes de fission et de fusion constants de leurs membranes extérieures et intérieures. Ces processus sont essentiels pour le maintien des fonctions mitochondriales essentielles telles que la phosphorylation oxydative ou la signalisation du calcium. D’un point de vue moléculaire, la fusion et la fission mitochondriale dépendent tous les deux des grandes GTPases de la famille des protéines de type dynamine. Les dynamines qui favorisent l’attachement et la fusion des membranes mitochondriales extérieures sont appelés les mitofusines.La mitofusine de la levure Fzo1 est une GTPase transmembranaire située dans la membrane externe de la mitochondrie. Son oligomérisation favorise l’attachement suivi de la fusion de la membrane externe mitochondriale. Fzo1 a été proposé récemment comme une protéine d’attachement potentielle entre les peroxysomes et les mitochondries lorsqu’elle est surexprimée. Cependant, on ignore si Fzo1 est présent sur les membranes peroxysomales dans les cellules sauvages ou si cette localisation extra-mitochondriale est une conséquence de la surexpression. De plus, nous ne savons toujours pas comment le Fzo1 peroxysomal et le Fzo1 mitochondrial interagissent dans ces contacts et quel est leur rôle dans la cellule. Durant ma thèse, j’ai pu prouver que Fzo1 se trouve réellement aux peroxysomes dans des conditions physiologiques et oligomérise avec le Fzo1 mitochondrial créant ainsi des contacts Fzo1-Fzo1 entre les peroxysomes et les mitochondries que nous appellerons maintenant des contacts « Permit Fzo1-dépendants ». On a découvert que ces contacts sont modulés par les niveaux de Fzo1 qui sont étroitement régulés par la ligase ubiquitine appelée Mdm30 mais aussi en fonction des niveaux de désaturation des acides gras dans la cellule. D’un point de vue fonctionnel et après avoir écarté plusieurs possibilités, nous avons trouvé que le rôle des contacts Permit Fzo1-dépendants est de réguler la fusion mitochondriale à travers le cycle glyoxylate, un processus qui permet aux cellules de convertir des composés unitaires de C2 en précurseurs de C4 pour la biosynthèse des acides aminés et des glucides. Nous avons découvert que les contacts Permit Fzo1-dépendants permettent le transfert mitochondrial des produits intermédiaires du cycle de glyoxylate pour stimuler la fusion mitochondriale. Ces résultats révèlent ainsi une réponse des organelles aux changements de désaturation des acides gras et aux besoins métaboliques de la cellule pour réguler la fusion mitochondriale.Enfin, les résultats obtenus au cours de ma thèse ont enrichi nos connaissances sur les contacts entre organelles et nous ont permis de prouver que Fzo1 est localisé sur les membranes mitochondriales et peroxysomales dans les cellules de type sauvage de levure. Nos études montrent également que les contacts Permit Fzo1-dépendants sont modulés en fonction des besoins de la cellule car ils jouent un rôle crucial dans l’entretien de la fusion mitochondriale en créant un raccourci possible pour les produits intermédiaires du cycle du glyoxylate pour atteindre les mitochondries lorsque cela est nécessaireMitochondria are highly dynamic organelles that undergo constant fission and fusion of their outer and inner membranes. These processes are critical to maintain essential mitochondrial functions such as oxidative phosphorylation or calcium signaling. On a molecular basis, mitochondrial fusion and fission both depend on large GTPases of the Dynamin-Related Protein (DRP) family. The DRPs that mediate attachment and fusion of mitochondrial outer membranes are called the Mitofusins. The yeast mitofusin Fzo1 is located in the mitochondrial outer membrane. Its oligomerization promotes mitochondrial tethering followed by mitochondrial outer membrane fusion. Fzo1 has recently been proposed as a potential tether between peroxisomes and mitochondria when overexpressed. However, whether Fzo1 is present on peroxisomal membranes in WT cells or whether this extra-mitochondrial localization is a consequence of overexpression is unknown. In addition, we still don’t know how peroxisomal and mitochondrial Fzo1 mediate these contacts and their purpose in the cell. In my thesis, we were able to prove that Fzo1 naturally localizes to peroxisomes and oligomerizes with the mitochondrial Fzo1 thus creating Fzo1-Fzo1 contacts between peroxisomes and mitochondria which we will now call “Fzo1-mediated permit” contacts. We found that these contacts are modulated by Fzo1 levels which are tightly regulated by an SCF ubiquitin ligase called Mdm30 but also depending on fatty acid desaturation levels in the cell. From a functional standpoint, we found that the role of Fzo1-mediated permit contacts is to regulate mitochondrial fusion through the glyoxylate cycle, a process which allows cells to convert C2 unit compounds to C4 precursors for amino acid and carbohydrate biosynthesis. We discovered that Fzo1-mediated permit contacts allow the mitochondrial transfer of early byproducts of the glyoxylate cycle to stimulate mitochondrial fusion. In fine, the results obtained during my thesis enriched our knowledge on organelle contacts and allowed us to prove that Fzo1 is localized on both mitochondrial and peroxisomal membranes in wild type cells. Our studies also show that Fzo1-mediated permit contacts are modulated according to the cell’s needs as they play a crucial role in upkeeping mitochondrial fusion by providing a possible shortcut for byproducts of the glyoxylate cycle to reach mitochondria when direly needed
Libros sobre el tema "Mitochondria fusion":
1
Zick, Michael. Roles of the isoforms of the dynamin-like GTPases Mgm1/OPA1 in mitochondrial fusion. 2011.
2
Hill, Geoffrey E. Mitonuclear Ecology. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780198818250.001.0001.
Resumen
Eukaryotes were born of a chimeric union of two prokaryotes. The legacy of this fusion is organisms with both a nuclear and mitochondrial genome that must work in a coordinated fashion to enable cellular respiration. The coexistence of two genomes in a single organism requires tight coadaptation to enable function. The need for coadaptation, the challenge of co-transmission, and the possibility of genomic conflict between mitochondrial and nuclear genes have profound consequences for the ecology and evolution of eukaryotic life. This book defines mitonuclear ecology as an emerging field that reassesses core concepts in evolutionary ecology in light of the necessity of mitonuclear coadaptation. I discuss and summarize research that tests new mitonuclear-based theories for the evolution of sex, two sexes, senescence, a sequestered germ line, speciation, sexual selection, and adaptation. The ideas presented in this book represent a paradigm shift for evolutionary ecology. Through the twentieth century, mitochondrial genomes were dismissed as unimportant to the evolution of complex life because variation within mitochondrial genomes was proposed to be functionally neutral. These conceptions about mitochondrial genomes and mitonuclear genomic interactions have been changing rapidly, and a growing literature in top journals is making it increasingly clear that the interactions of the mitochondrial and nuclear genomes over the past 2 billion years have played a major role in shaping the evolution of eukaryotes. These new hypotheses for the evolution of quintessential characteristics of complex life hold the potential to fundamentally reshape the field of evolutionary ecology and to inform the emerging fields of mitochondrial medicine and mitochondrial-based reproductive therapies.
3
Hinder, Lucy M., Kelli A. Sullivan, Stacey A. Sakowski y Eva L. Feldman. Mechanisms Contributing to the Development and Progression of Diabetic Polyneuropathy. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0114.
Resumen
Advances in our understanding of diabetes in human patients and experimental models indicate that a number of mechanisms may contribute to sensory nerve damage in diabetic polyneuropathy (DPN). In addition to oxidative stress, hyperglycemia and hyperlipidemia, recent research in pain, advanced glycation endproduct (AGE), and proteomics specify a contributory role for altered neuronal calcium homeostasis in DPN. Technology advances indicate neuronal energy balance and mitochondrial biogenesis, fission, and fusion are additional potential mechanisms. The effects of dysregulation or loss of insulin signaling and the effects of glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are also implicated.
Capítulos de libros sobre el tema "Mitochondria fusion":
1
Ichikawa, H., L. Tanno-Suenaga y J. Imamura. "Transfer of Mitochondria Through Protoplast Fusion". En Plant Protoplasts and Genetic Engineering II, 360–75. Berlin, Heidelberg: Springer Berlin Heidelberg, 1989. http://dx.doi.org/10.1007/978-3-642-74454-9_21.
2
Kennedy, Barry E., Mark Charman y Barbara Karten. "Measurement of Mitochondrial Cholesterol Import Using a Mitochondria-Targeted CYP11A1 Fusion Construct". En Methods in Molecular Biology, 163–84. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-6875-6_12.
3
Karbowski, Mariusz. "Mitochondria on Guard: Role of Mitochondrial Fusion and Fission in the Regulation of Apoptosis". En Advances in Experimental Medicine and Biology, 131–42. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-1-4419-6706-0_8.
4
Griparic, Lorena, Brian Head y Alexander M. van der Bliek. "Mitochondrial fission and fusion machineries". En Mitochondrial Function and Biogenesis, 227–49. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/b95718.
5
Meeusen, Shelly L. y Jodi Nunnari. "Mitochondrial Fusion In Vitro". En Methods in Molecular Biology, 461–66. Totowa, NJ: Humana Press, 2007. http://dx.doi.org/10.1007/978-1-59745-365-3_32.
6
Chan, Eliana Y. L., Jarungjit Rujiviphat y G. Angus McQuibban. "The Genetics of Mitochondrial Fusion and Fission". En Mitochondrial Dynamics and Neurodegeneration, 1–46. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-1291-1_1.
7
Giannakis, Konstantinos y Theodore Andronikos. "Mitochondrial Fusion Through Membrane Automata". En Advances in Experimental Medicine and Biology, 163–72. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-09012-2_10.
8
Lenaers, Guy, Dominique Bonneau, Cécile Delettre, Patrizia Amati-Bonneau, Emmanuelle Sarzi, Dan Miléa, Christophe Verny, Vincent Procaccio, Christian Hamel y Pascal Reynier. "Neurological Diseases Associated with Mutations in the Mitochondrial Fusion Machinery". En Mitochondrial Dynamics and Neurodegeneration, 169–96. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-1291-1_6.
9
Chu, Charleen T. y Sarah B. Berman. "Mitochondrial Fission-Fusion and Parkinson’s Disease: A Dynamic Question of Compensatory Networks". En Mitochondrial Dynamics and Neurodegeneration, 197–213. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-1291-1_7.
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Samanas, Nyssa Becker y Suzanne Hoppins. "Cell-Free Analysis of Mitochondrial Fusion by". En Methods in Molecular Biology, 129–40. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0676-6_10.
Actas de conferencias sobre el tema "Mitochondria fusion":
1
Waggoner, AA, A. Wright, T. Moore, SA Gebb, J. King, G. Wilson y MN Gillespie. "A Fusion Protein Construct Targeting a DNA Repair Enzyme to Mitochondria Protects Against Oxidant-Induced Edema Formation in Perfused Rat Lungs." En American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a5559.
2
Chouteau, Joshua, Olena Gorodnya, Mykhaylo Ruchko, Boniface Obiako, Glenn Wilson y Mark N. Gillespie. "Novel Fusion Protein Constructs Targeting DNA Repair Enzymes To Mitochondria Protect Against Pseudomonas Aeruginosa-Induced Acute Lung Injury In Intact Rats". En American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado. American Thoracic Society, 2011. http://dx.doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a3763.
3
Suzuki, Sozo, Kazuo Mori, Koji Sugai, Yasuyuki Akutsu, Masaaki Ishikawa, Hideaki Sakai y Katsuhide Hiwatashi. "ELECTRONMICROSCOPIC STUDIES ON PLATELETS AND MEGAKARYOCYTES IN GIANT PLATELET SYNDROME". En XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644560.
Resumen
Giant platelet syndrome are characterized morphologically by many giant platelets associated with several functional abnormalities in the peripheral blood. However, the mechanism of large platelet production has not yet been clarified. In 1981, we reported acase with Bernard-Soulier syndrome(BSS) in whom giant platelets were considered to be formed by fusion of two or three platelets in the circulating blood. We examined the ultrastructure of platelets and megakaryocytes in another case with BSS (29 year-old female) and a case with May-Hegglin anomaly (31 year-old male). Whole blood and bone marrow specimens were fixed with glutaraldehyde-osmium solution. Thin sections were prepared and stained with uranyl acetate and lead cytrate. Membrane systems of platelets and megakaryocytes in a case with BSS was investigated by staining of surface coating with ruthenium red.In a case with BSS, most platelets were very large and similar in morphology to those in formerly reported case. Giant platelets contained several-fold increased number of α-granules and mitochondria. Typical dense bodies were also observed. Contents of ATP/ADP, platelet factor-4(PF-4), B-thromboglobulin(B-TG) and platelet factor-3 availability(PF-3) were increased. Disorganization of microtubules was recognized. Some giant platelet contained membrane systems similar to demarcation membranes(DM) in megakaryocytes, characteristically. In mature megakaryocytes, areas divided by DM similar in size to those in normal megakaryocytes were observed. Several of these areas appeared to fuse together to form the giant platelets containing many granules and remnants of DM. In a case with May-Hegglin anomaly, typical Dohle’s bodies were shown in neutrophilic granulocytes. Giant platelets in this case also contained large number of α-granules and some of them contained membrane systems similar to DM. Areas similar in morphology to these giant platelets were clearly noted in the cytoplasm of mature megakaryocytes.In these cases, most giant platelets in the peripheral blood may be formed in the cytoplasm of megakaryocytes by fusion of several areas divided by DM, each of which may become normal sized platelets in normal megakaryocytes.
4
Schwarz, Johannes y Oliver Eickelberg. "Mitochondrial Fusion Processes Modulate Lung Fibroblast Activation". En American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1926.
5
Kim, So Ri, Yong Chul Lee, Hae Jin Park, Dong Im Kim y Soon Ha Kim. "Mitochondrial fusion in the pathogenesis of severe asthma with fungal sensitization". En ERS International Congress 2016 abstracts. European Respiratory Society, 2016. http://dx.doi.org/10.1183/13993003.congress-2016.pa1082.
6
Chang, Zee-Fen. "Abstract 1402: NME3 links mitochondrial fusion to DNA repair in nuclear genome". En Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-1402.
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Graves, J. Anthony, Kristi D. Rothermund, Yudong Wang, Jennifer Elster, Jerry Vockley, Bennett Van Houten y Edward V. Prochownik. "Abstract 1259: c-Myc influences mitochondrial structure and function by regulating fusion and fission". En Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-1259.
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Arumugam, P. I., M. Wessendarp, Y. Ma, M. Imbrogno, M. Collins, B. C. Carey, J. Stock, C. Chalk, B. C. Trapnell y M. D. Filippi. "GM-CSF Is Required for Regulation of Mitochondrial Fusion, Fission, and Mitophagy in Macrophages". En American Thoracic Society 2024 International Conference, May 17-22, 2024 - San Diego, CA. American Thoracic Society, 2024. http://dx.doi.org/10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2600.
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Nguyen, Nicholas D., Meifang Yu, Tara N. Fujimoto, Abagail Delahoussaye, Yanqing Huang, Manuel A. Estrada y Cullen M. Taniguchi. "Abstract 555: Mitochondrial fusion exertsKRAS-dependent therapeutic synergy with gemcitabine/nab-paclitaxel in preclinical models of pancreatic cancer". En Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-555.
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Lyu, Mi-Ae, Lawrence H. Cheung, John W. Marks y Michael G. Rosenblum. "Abstract 2579: Bax345/BLyS: A novel, completely human fusion construct targeting malignant B cells and delivering a unique mitochondrial toxin". En Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-2579.
Informes sobre el tema "Mitochondria fusion":
1
Izhar, Shamay, Maureen Hanson y Nurit Firon. Expression of the Mitochondrial Locus Associated with Cytoplasmic Male Sterility in Petunia. United States Department of Agriculture, febrero de 1996. http://dx.doi.org/10.32747/1996.7604933.bard.
Resumen
The main goal of the proposed research was to continue the mutual investigations into the molecular basis of CMS and male fertility restoration [MRF], with the ultimate goal of understanding these phenomena in higher plants. The experiments focused on: (1) dissecting apart the complex CMS - specific mitochondrial S-Pcf locus, in order to distinguish its essential parts which cause sterility from other parts and study its molecular evolution. (2) Studying the expression of the various regions of the S-Pcf locus in fertile and sterile lines and comparing the structure and ultrastructure of sterile and fertile tissues. (3) Determine whether alteration in respiration is genetically associated with CMS. Our mutual investigations further substantiated the association between the S-Pcf locus and CMS by the findings that the fertile phenotype of a population of unstable petunia somatic hybrids which contain the S-Pcf locus, is due to the presence of multiple muclear fertility restoration genes in this group of progenies. The information obtained by our studies indicate that homologous recombination played a major role in the molecular evolution of the S-Pcf locus and the CMS trait and in the generation of mitochondrial mutations in general. Our data suggest that the CMS cytoplasm evolved by introduction of a urs-s containing sublimon into the main mitochondrial genome via homologous recombination. We have also found that the first mutation detected so far in S-Pcf is a consequence of a homologous recombination mechanism involving part of the cox2 coding sequence. In all the cases studied by us, at the molecular level, we found that fusion of two different cells caused mitochondrial DNA recombination followed by sorting out of a specific mtDNA population or sequences. This sequence of events suggested as a mechanism for the generation of novel mitochondrial genomes and the creation of new traits. The present research also provides data concerning the expression of the recombined and complex CMS-specific S-Pcf locus as compared with the expression of additional mitochondrial proteins as well as comparative histological and ultrastructural studies of CMS and fertile Petunia. Evidence is provided for differential localization of mitochondrially encoded proteins in situ at the tissue level. The similar localization patterns of Pcf and atpA may indicate that Pcf product could interfere with the functioning of the mitochondrial ATPase in a tissue undergoing meiosis and microsporogenesis. Studies of respiration in CMS and fertile Petunia lines indicate that they differe in the partitioning of electron transport through the cytochrome oxidase and alternative oxidase pathways. The data indicate that the electron flux through the two oxidase pathways differs between mitochondria from fertile and sterile Petunia lines at certain redox states of the ubiquinone pool. In summary, extensive data concerning the CMS-specific S-Pcf locus of Petunia at the DNA and protein levels as well as information concerning different biochemical activity in CMS as compared to male fertile lines have been accumulated during the three years of this project. In addition, the involvement of the homologous recombination mechanism in the evolution of mt encoded traits is emphasized.
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Granot, David, Richard Amasino y Avner Silber. Mutual effects of hexose phosphorylation enzymes and phosphorous on plant development. United States Department of Agriculture, enero de 2006. http://dx.doi.org/10.32747/2006.7587223.bard.
Resumen
Research objectives 1) Analyze the combined effects of hexose phosphorylation and P level in tomato and Arabidopsis plants 2) Analyze the combined effects of hexose phosphorylation and P level in pho1 and pho2 Arabidopsis mutants 3) Clone and analyze the PHO2 gene 4) Select Arabidopsis mutants resistant to high and low P 5) Analyze the Arabidopsis mutants and clone the corresponding genes 6) Survey wild tomato species for growth characteristics at various P levels Background to the topic Hexose phosphorylating enzymes, the first enzymes of sugar metabolism, regulate key processes in plants such as photosynthesis, growth, senescence and vascular transport. We have previously discovered that hexose phosphorylating enzymes might regulate these processes as a function of phosphorous (P) concentration, and might accelerate acquisition of P, one of the most limiting nutrients in the soil. These discoveries have opened new avenues to gain fundamental knowledge about the relationship between P, sugar phosphorylation and plant development. Since both hexose phosphorylating enzymes and P levels affect plant development, their interaction is of major importance for agriculture. Due to the acceleration of senescence caused by the combined effects of hexose phosphorylation and P concentration, traits affecting P uptake may have been lost in the course of cultivation in which fertilization with relatively high P (30 mg/L) are commonly used. We therefore intended to survey wild tomato species for high P-acquisition at low P soil levels. Genetic resources with high P-acquisition will serve not only to generate a segregating population to map the trait and clone the gene, but will also provide a means to follow the trait in classical breeding programs. This approach could potentially be applicable for other crops as well. Major conclusions, solutions, achievements Our results confirm the mutual effect of hexose phosphorylating enzymes and P level on plant development. Two major aspects of this mutual effect arose. One is related to P toxicity in which HXK seems to play a major role, and the second is related to the effect of HXK on P concentration in the plant. Using tomato plants we demonstrated that high HXK activity increased leaf P concentration, and induced P toxicity when leaf P concentration increases above a certain high level. These results further support our prediction that the desired trait of high-P acquisition might have been lost in the course of cultivation and might exist in wild species. Indeed, in a survey of wild species we identified tomato species that acquired P and performed better at low P (in the irrigation water) compared to the cultivated Lycopersicon esculentum species. The connection between hexose phosphorylation and P toxicity has also been shown with the P sensitive species VerticordiaplumosaL . in which P toxicity is manifested by accelerated senescence (Silber et al., 2003). In a previous work we uncovered the phenomenon of sugar induced cell death (SICD) in yeast cells. Subsequently we showed that SICD is dependent on the rate of hexose phosphorylation as determined by Arabidopsis thaliana hexokinase. In this study we have shown that hexokinase dependent SICD has many characteristics of programmed cell death (PCD) (Granot et al., 2003). High hexokinase activity accelerates senescence (a PCD process) of tomato plants, which is further enhanced by high P. Hence, hexokinase mediated PCD might be a general phenomena. Botrytis cinerea is a non-specific, necrotrophic pathogen that attacks many plant species, including tomato. Senescing leaves are particularly susceptible to B. cinerea infection and delaying leaf senescence might reduce this susceptibility. It has been suggested that B. cinerea’s mode of action may be based on induction of precocious senescence. Using tomato plants developed in the course of the preceding BARD grant (IS 2894-97) and characterized throughout this research (Swartzberg et al., 2006), we have shown that B. cinerea indeed induces senescence and is inhibited by autoregulated production of cytokinin (Swartzberg et al., submitted). To further determine how hexokinase mediates sugar effects we have analyzed tomato plants that express Arabidopsis HXK1 (AtHXK1) grown at different P levels in the irrigation water. We found that Arabidopsis hexokinase mediates sugar signalling in tomato plants independently of hexose phosphate (Kandel-Kfir et al., submitted). To study which hexokinase is involved in sugar sensing we searched and identified two additional HXK genes in tomato plants (Kandel-Kfir et al., 2006). Tomato plants have two different hexose phosphorylating enzymes; hexokinases (HXKs) that can phosphorylate either glucose or fructose, and fructokinases (FRKs) that specifically phosphorylate fructose. To complete the search for genes encoding hexose phosphorylating enzymes we identified a forth fructokinase gene (FRK) (German et al., 2004). The intracellular localization of the four tomato HXK and four FRK enzymes has been determined using GFP fusion analysis in tobacco protoplasts (Kandel-Kfir et al., 2006; Hilla-Weissler et al., 2006). One of the HXK isozymes and one of the FRK isozymes are located within plastids. The other three HXK isozymes are associated with the mitochondria while the other three FRK isozymes are dispersed in the cytosol. We concluded that HXK and FRK are spatially separated in plant cytoplasm and accordingly might play different metabolic and perhaps signalling roles. We have started to analyze the role of the various HXK and FRK genes in plant development. So far we found that LeFRK2 is required for xylem development (German et al., 2003). Irrigation with different P levels had no effect on the phenotype of LeFRK2 antisense plants. In the course of this research we developed a rapid method for the analysis of zygosity in transgenic plants (German et al., 2003).
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Sadot, Einat, Christopher Staiger y Mohamad Abu-Abied. Studies of Novel Cytoskeletal Regulatory Proteins that are Involved in Abiotic Stress Signaling. United States Department of Agriculture, septiembre de 2011. http://dx.doi.org/10.32747/2011.7592652.bard.
Resumen
In the original proposal we planned to focus on two proteins related to the actin cytoskeleton: TCH2, a touch-induced calmodulin-like protein which was found by us to interact with the IQ domain of myosin VIII, ATM1; and ERD10, a dehydrin which was found to associate with actin filaments. As reported previously, no other dehydrins were found to interact with actin filaments. In addition so far we were unsuccessful in confirming the interaction of TCH2 with myosin VIII using other methods. In addition, no other myosin light chain candidates were found in a yeast two hybrid survey. Nevertheless we have made a significant progress in our studies of the role of myosins in plant cells. Plant myosins have been implicated in various cellular activities, such as cytoplasmic streaming (1, 2), plasmodesmata function (3-5), organelle movement (6-10), cytokinesis (4, 11, 12), endocytosis (4, 5, 13-15) and targeted RNA transport (16). Plant myosins belong to two main groups of unconventional myosins: myosin XI and myosin VIII, both closely related to myosin V (17-19). The Arabidopsis myosin family contains 17 members: 13 myosin XI and four myosin VIII (19, 20). The data obtained from our research of myosins was published in two papers acknowledging BARD funding. To address whether specific myosins are involved with the motility of specific organelles, we cloned the cDNAs from neck to tail of all 17 Arabidopsis myosins. These were fused to GFP and used as dominant negative mutants that interact with their cargo but are unable to walk along actin filaments. Therefore arrested organelle movement in the presence of such a construct shows that a particular myosin is involved with the movement of that particular organelle. While no mutually exclusive connections between specific myosins and organelles were found, based on overexpression of dominant negative tail constructs, a group of six myosins (XIC, XIE, XIK, XI-I, MYA1 and MYA2) were found to be more important for the motility of Golgi bodies and mitochondria in Nicotiana benthamiana and Nicotiana tabacum (8). Further deep and thorough analysis of myosin XIK revealed a potential regulation by head and tail interaction (Avisar et al., 2011). A similar regulatory mechanism has been reported for animal myosin V and VIIa (21, 22). In was shown that myosin V in the inhibited state is in a folded conformation such that the tail domain interacts with the head domain, inhibiting its ATPase and actinbinding activities. Cargo binding, high Ca2+, and/or phosphorylation may reduce the interaction between the head and tail domains, thus restoring its activity (23). Our collaborative work focuses on the characterization of the head tail interaction of myosin XIK. For this purpose the Israeli group built yeast expression vectors encoding the myosin XIK head. In addition, GST fusions of the wild-type tail as well as a tail mutated in the amino acids that mediate head to tail interaction. These were sent to the US group who is working on the isolation of recombinant proteins and performing the in vitro assays. While stress signals involve changes in Ca2+ levels in plants cells, the cytoplasmic streaming is sensitive to Ca2+. Therefore plant myosin activity is possibly regulated by stress. This finding is directly related to the goal of the original proposal.