Дисертації з теми "Apoptose mitochondriale"
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Aure, Karine. "Physiopathologie moléculaire et cellulaire des maladies mitochondriales à présentation neurologique." Paris 6, 2007. http://www.theses.fr/2007PA066281.
Landes, Thomas. "Dynamique mitochondriale et apoptose : rôle de l'interaction entre Opa1 et Bnip3." Toulouse 3, 2009. http://thesesups.ups-tlse.fr/671/.
Mitochondria are highly dynamic organelles that continually fuse and divide. Several studies suggest a link between mitochondrial dynamics and the intrinsic pathway of apoptosis, mediated by members of the Bcl-2 family, leading to the release of apoptogenic proteins, including cytochrome c, from the mitochondrial intermembrane space into the cytosol. We have previously identified Opa1 a dynamin of the inner membrane that regulates mitochondrial fusion. More recently, Opa1 has also been proposed to control, during apoptosis, cytochrome c redistribution through its capacity to locally form oligomers at mitochondrial cristae junctions. In this study, we identified Bnip3, a mitochondrial pro-apoptotic BH3-only protein of the Bcl-2 family, as a physical and functional partner of Opa1. Overall, our results give some insight into the relationship between mitochondrial dynamics and apoptosis and, in the future, may help to understand the aetiology of autosomal dominant optic atrophy, caused by Opa1 mutations
Desbourdes, Céline. "Nucléoside diphosphate kinase D : une protéine mitochondriale bifonctionnelle." Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAV004/document.
The nucleoside diphosphate kinases (NDPK) are essential for generation of nucleoside triphosphates (NTPs) using ATP and NDPs. The mitochondrial NDPK isoform (NDPK-D) located in the mitochondrial intermembrane space is found to have two modes of function. First, the phosphotransfer mode in which the protein has a kinase activity like other NDPK enzymes. In this mode, NDPK-D produces GTP for the optic atrophy 1 protein (OPA1), a GTPase involved in mitochondrial fusion, and ADP for the adenylate translocator (ANT) and the mitochondrial ATPase for ATP regeneration. The second mode of function is called lipid transfer and is related to the capacity of NDPK-D to bind anionic phospholipids, especially cardiolipin (CL). In this mode, the protein can cross-link the two mitochondrial membranes and transfer CL from the inner to the outer mitochondrial membrane, which can serve as a signal for mitophagy and apoptosis. This work aims to study these NDPK-D functions in more detail. With the use of HeLa cells stably expressing the wild-type, kinase inactive (H151N mutation) or lipid binding deficient (R90D mutation) NDPK-D and mouse lung epithelial cells, we show (i) the close proximity between NDPK-D and OPA1 that leads to GTP channeling from NDPK-D to OPA1, (ii) the essential role of NDPK-D for CL externalization to the mitochondrial surface during mitophagy, serving as a recognition signal for LC3-II-autophagosomes to eliminate damaged mitochondria, (iii) the possible inhibition of CL externalization due to the presence of NDPK-D/OPA1 complexes, and (iv) a pro-metastatic phenotype of HeLa cells expressing either of the NDPK-D mutants (H151N or R90D), characterized by high invasive and migratory potential, altered proteomic profile and changed mitochondrial network structure and function. Finally, a first bacterial expression and purification strategy for full-length OPA1 has been established for future in vitro studies of NDPK-D/OPA1 complexes
Olichon, Aurélien. "Morphologie mitochondriale : fonctions et dysfonctions de la dynamine humaine OPA1." Toulouse 3, 2004. http://www.theses.fr/2004TOU30295.
Mitochondria are essential organelles that provide energy to the cell and act as reservoirs of apoptogenic molecules. Mitochondrial morphology and dynamics are crucial for their function and their transmission, and drastically change during apoptosis. To explain the dynamic of the mitochondrial network morphology, a model conserved from yeast to human proposes that two antagonistic forces, fission versus fusion, are monitored by proteins localized on the mitochondrial outer membrane, such as Dnm1/DRP-1 or Fzo1/Mfn1-2. Conversely, dynamic of the inner membrane is largely unknown. Data on the large GTPase Msp1 in S. Pombe, OPA1 in human, and Mgm1 in S. Cerevisiae suggest that this dynamin related protein is involved in the inner-membrane structure and dynamic. We have isolated the OPA1 gene sequence encoding a human dynamin. Moreover, we have shown that OPA1 gene is mutated in patients suffering from an hereditary optic neuropathy leading to blindness (ADOA: Autosomal Dominant Optic Atrophy, OMIM 165500) My thesis project was to characterize OPA1 function in order to understand its dysfunction, impact on mitochondrial dynamics and function, and especially answer some questions about the pathological process of the ADOA. Orthology between OPA1 and Msp1 was confirmed by showing that OPA1 complements the lethal msp1 gene deletion in fission yeast. Using both biochemical and cytological approaches we have precisely localized OPA1 strongly associated with the inner membrane of the mitochondria, facing the innermembrane space. To investigate OPA1 dynamin function, we used total or selective downregulation or over-expression of wild type OPA1 variants or mutant, and showed that OPA1 could function in the inner-membrane dynamics and could have a role in structuring the cristae membrane. This later structural role suggests that OPA1 could be a key regulator of the mobilization of cytochrome c by remodeling the cristae membrane
Singh, François. "Skeletal muscle toxicity and statins : role of mitochondrial adaptations." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ050/document.
Although statins are the most prescribed class of lipid-lowering agents, adverse muscular toxicity has been reported, which can lead to the appearance of a myopathy. In the first part, we showed in Humans and animals that statins inhibit directly the mitochondrial respiratory chain, and induce the production of reactive oxygen species (ROS), that trigger apoptotic pathways in glycolytic skeletal muscles, whereas oxidative muscles are not impaired. We then showed in vitro that reductive stress can provoke mitochondrial oxidation, that could lead to an activation of mitochondrial biogenesis pathways. Moreover, the consequent increase in mitochondrial content enabled to protect cells against statin-induced apoptosis. Finally, we showed in vivo that the induction of mitochondrial biogenesis is necessary for statin tolerance in oxidative skeletal muscles. In conclusion, mitochondrial phenotype, both quantitatively and qualitatively, seems to be a key factor in the appearance of statin myopathy
Ferré, Cécile. "Mécanismes moléculaires et cellulaires à la base du pouvoir neuroprotecteur de la protéine "mitochondriale" X du bornavirus." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30049/document.
Bornavirus, a non-cytolytic RNA virus establishes a long-lasting persistence in the central nervous system of infected animals. Viral persistence is facilitated by the expression of the non-structural X protein, which is addressed both to nucleus and mitochondria, where it interferes both with cellular antiviral responses and the initiation of apoptosis. Our team recently reported that the singled-out expression of the X protein could protect neurons against toxins of the mitochondrial respiratory chain, both in vitro and in a mouse model of Parkinson's disease (PD). During my Ph.D., we further demonstrated that the X protein triggered enhanced filamentation of the mitochondrial network, in physiological as well as in oxidative stress conditions. This effect is particularly interesting when considering the importance of mitochondrial dynamics in the pathophysiology of neurodegenerative diseases. Even if the therapeutic potential of this viral protein is now well established, the underlying molecular and cellular mechanisms are far from being elucidated. It is however clear that neuroprotection conferred by the X protein is strictly dependent on its mitochondrial localization. In this context, the goal of my Ph.D. project was to clarify the molecular mechanisms whereby the X protein is targeted to mitochondria and/or to the nucleus, in link with its protective capabilities. We focused on the amino terminal residues of X, by performing fusion proteins of various forms of these residues with GFP and by analyzing their cellular localization. We demonstrated that this region contains overlapping and interdependent signals for nuclear localization, nuclear export and mitochondrial targeting of the X protein. We also identified a point mutation or deletion leading to an almost exclusively mitochondrial localization of the X protein. As a consequence, these X mutants exhibited a better neuroprotective function. In order to get further insight into X-mediated neuroprotection, we also searched for the cellular partners of X in mitochondria. We revealed a direct and specific interaction of the X protein with the chaperone Hspa9, a protein that was recently shown to be involved in neurodegenerative diseases, notably in PD's patients. We observed that the down-regulation of Hspa9 triggered by mitochondrial toxins was attenuated by the coexpression of X, suggesting a functional link between these two proteins. We also demonstrated that Hspa9 overexpression could protect neurons from mitochondrial dysfunctions, similarly to the X protein. Altogether, these results have contributed to a better understanding of the mechanisms underlying the neuroprotective potential of the X protein, which may favor the development of novel therapeutic strategies
Carré, Manon. "Agents anti-tubuline et apoptose : du cytosquelette microtubulaire à la tubuline mitochondriale." Aix-Marseille 2, 2004. http://www.theses.fr/2004AIX22955.
Martel, Cécile. "Rôle de la perméabilité membranaire mitochondriale, de la phosphorylation de VDAC et de la signalisation de l’apoptose dans la pathogenèse de la stéatose hépatique." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T075.
Non-alcoholic steatosis is a liver disease characterized by lipid accumulation in the cytoplasm of hepatocytes. For a long time, it has been considered as a benign condition. Now it is known that it can precede the development of a severe stage, non-alcoholic steatohepatitis (NASH). NASH is accompanied by severe dammages of the liver linked to the genesis of oxidative stress, inflammation and cell death. Mitochondrion is a central player of this disease; however, the knowledge of mitochondrial dysfunction and its consequences on apoptosis is still insufficient. Indeed, mitochondria are responsible for lipid degradation by -oxidation. Mitochondria act as a central integrator of apoptotic signals by triggering the mitochondrial membrane permeabilization (MMP) leading to the release of apoptogenic factors. This process is considered as the point of no return of the mitochondrial pathway of apoptosis. We aimed to better understand the molecular mechanisms linking mitochondrial liver apoptosis and steatosis. Combination of four experimental models of steatosis (human biopsies, isolated mitochondria from ob/ob obese mice, high fat diet-fed mice or hepatic cell lines) displayed, in steatotic livers, increased sensitivity to MMP induction and permeability of VDAC (Voltage dependent anion channel), a protein which forms a channel in the outer mitochondrial membrane. These findings are associated with the hypo-phosphorylation of VDAC on a threonine residue and the loss of its interaction with the anti-apoptotic Bcl-XL and GSK3 kinase, thus revealing a new lipid-induced signaling pathway. Our work is based on the use of functional assays on isolated mitochondria that we have developed and validated in several studies involving various strategies. To conclude, our study increases the knowledge on the lipid-induced mitochondrial weakness preceding hepatic apoptosis and opens perspectives in biomedical applications
Jelinek, Antje. "In-vitro-Toxizität grenzflächenaktiver Substanzen Wirkung auf Zellmembran, mitochondriale Funktion und Apoptose /." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963587676.
Lefevre, Sophie. "Modèle levure de l'ataxie de Friedreich : stress oxydant, apoptose et dynamique mitochondriale." Paris 6, 2010. http://www.theses.fr/2010PA066204.
Cisbani, Giulia. "PARL et HAX1 dans la régulation de l'activité mitochondriale." Thesis, Université Laval, 2010. http://www.theses.ulaval.ca/2010/26847/26847.pdf.
Scholtes, Charlotte. "Étude des liens entre les acteurs de la dynamique mitochondriale et l'apoptose dans la dégénérescence musculaire dystrophinedépendante chez Caenorhabditis elegans." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1001.
Mitochondrial shape is continually changing thanks to the combined actions of fission and fusion events making the mitochondrial network very dynamic. The mitochondrial fission and fusion processes are finely regulated by GTPases of the family of dynamins that are well conserved between species. In C. elegans, fission is regulated by DRP-1, fusion of the inner membrane by EAT-3, homologue of OPA1, and fusion of the outer membrane by FZO-1, homologue of MFN1. In the muscle cells of wild nematode, tubular and circular mitochondria are in equal proportions and organized along the sarcomere. However, during dystrophin-dependent muscle degeneration, fragmentation of the mitochondrial network in muscle cells occurs. But the role of the actors of mitochondrial dynamics in the molecular mechanisms leading to dystrophin-dependent muscle degeneration is still misunderstood. We found that: (i) dystrophin-dependent muscle degeneration was accompanied by a drastic increase in mitochondrial fragmentation that can be saved by genetic manipulation of mitochondrial dynamics (ii) loss of function of the fission gene drp-1 or overexpression of the eat-3 and fzo-1 fusion genes causes a reduction in muscle degeneration and improved mobility of dystrophic mutants (iii) DRP-1 functions in apoptosis and other are important for the death of dystrophin-deficient muscle cells (iv) The involvement of DRP-1 in apoptosis is also important for age-dépendant muscle degeneration. In conclusion, our results point toward a mechanism involving mitochondrial dynamics to impact muscle degeneration via apoptosis in Caenorhabditis elegans
Nsoure, Obame Fatou. "Permeabilité membranaire mitochondriale et protection du myocarde lors de l'ischemie-reperfusion experimentale." Paris 11, 2009. http://www.theses.fr/2009PA114811.
Myocradial ischemia-reperfusion injuries require cardiprotective approaches to improve the repermeabilization of coronaries arteries. So in this work we looked at the mitochondrial permeability transition pore (mPTP) inhibition as this pore is implicated in ischemia-reperfusion injury. We used two pharmalogical strategies to inhibit it. (i) the first one targeted a mitonchondrial outer membrane receptor, the peripheral benzodiazepine (PBR), which is a putative component of mPTP. The cardioprotectio, mediated by PBR was evaluated by 4'-chlorodiazépam (CDZ) a specific PBR ligand. We used a model of global ischemia-reperfusion in isolated rat hearts and a model of regional myocardial ischemia-reperfusion in anaestheized rat. We showed that CDZ reduced infarct size afetr ischemia-reperfusion, improved mitochondrial funcions and decreased apotosis. We observed a reduction of cytochrome C and apoptosis inducing factors (AIF) release with a limitation of membrane permeability and with mPTP inhibition. We also demonstrated that this effect was related to a modification of the balance of the Bel-2 family proteins at the level of the mitochondrial outer member. Indeed, DCZ stabilized the association of bel-2 with the mitochondrial membrane and reduced the interaction of Bax. (ii) The second strategy aimed at stimulation the reperfusion injury salavage kinase (RISK), an endogenous protection cascade implied in pre and postconditioning, asthe cardioprotective effect mediated by RISK was suggested to be linked to mPTP inhibition. We used morphine a well-known cardioprotective opioid ligand which was shown to activated the RISK pathway and to inihibit glycogen synthase kinase -3beta (GSK-3beta). We showed that morphine reduced infarct size in a model of regional myocardial ischemia-reperfusion in rats improved mitochondrials functions. This cardioprotective effect was confirmed in isolated adult rat cardiomyocytes subjected to anoxia-reoxygenation as morphine delayed mPTP opening and increased cell survival. The protection afforded by morphine in vitro and in vivo was mimicked by the GSK-3Beta inhibitor SB16763, and was abolished by mortmannine a PI3K inhibitor. These results confirmed the involvement of the RISK pathway in the cardioprotective effect of both morphine and SB216763 and demonstrated a link between this pathway and mPTP inhibition. In a last part we showed that these two strategies had in common an antioxydant effect which appears necessary ti inhibit mPTP and to protect cardiomyocytes. Taken together these results demonstrate and pharmacological strategy limiting the mitochondrial permeability acting on mPTP is essential to protect the myocardium
Malissein, Emilie. "Physiologie mitochondriale et apoptose couplée à la signalisation du récepteur à l'antigène des lymphocytes B." Limoges, 2005. http://aurore.unilim.fr/theses/nxfile/default/d34a6617-a544-4cab-8d1a-a6725a6a863f/blobholder:0/2005LIMO0009.pdf.
BCR signaling presents differential functional responses, dependent of B cell stage of differentiation. The pro-apoptotic activity of Bad protein and its intracellular traffic are regulated by phosphorylation and dephosphorylation. Modulation of Bad phosphorylation during BCR-induced apoptosis and correlation with cell death mitochondrial pathway are not fully characterized. We show by flow cytometry, immunoprecipitation, Western Blotting and confocal microscopy that : (i) Bad activation (dephosphorylation) is implicated in BCR-induced apoptosis of immature B lymphocytes (ii) regulation of Bad phosphorylation status may contribute to BCR functional duality (survival/apoptosis) (iii) differential subcellular compartmentalization of Bad (in particular in rafts) may contribute to sensitize immature B cells to apoptosis
Gomez, Ludovic. "Transition de perméabilité mitochondriale : des lésions induites par l'ischémie-reperfusion au rejet du greffon cardiaque." Lyon 1, 2006. http://www.theses.fr/2006LYO10067.
Belzacq, Anne-Sophie. "La voie mitochondriale de l'apoptose, identification d'une nouvelle cible thérapeutique potentielle : le translocateur de nucléotides à adénine (ANT)." Compiègne, 2002. http://www.theses.fr/2002COMP1408.
Arachiche, Amal. "Recherche des signaux effecteurs dans l'exposition membranaire de la phosphatidylsérine procoagulante : exploration des voies MAPK/ERK et pro-apoptotique mitochondriale." Paris 7, 2009. http://www.theses.fr/2009PA077090.
Phosphatidylserine (PS) exposure at the surface of activated platelets or cells is important in coagulation. Indeed, exposed PS can promote assembly and activation of the coagulation factors. Impaired PS exposure can be responsible for bleeding events, as in Scott syndrome, while excessive PS exposure leads to thrombotic events. PS exposure also occurs at the membrane of apoptotic cells, and is essential for their clearance by phagocytes. The aim of this work was to identify in hematopoietic cells (platelets and lymphocytic cell lines) the molecular mechanisms controlling the rapid Ca²⁺-dependent PS exposure. Understanding this mechanism is essential to modulate PS exposure in thrombotic disorders. In this work, the involvement in PS exposure of the MAPK/ERK pathway, and the hypohesis that the process is a rapid apoptotic phenomenon controlled by loss of mitochondrial transmembrane potential (ΔΨm) were examined. The results show that although they may occur concurrently, neither the MAPK/ERK pathway activation, nor the loss of A\|/m control the rapid procoagulant PS exposure. The data also highlight the key role of an increase in intracellular Ca²⁺ brought about by a massive influx in the process. Therefore, the importance of other factors associated to (and dependent on) Ca²⁺ influx must be analyzed, such as activation of membrane ion channels (K⁺, Na⁺. . . ), which has been shown to influence phospholipid membrane remodelling in different cells models
Vazeille, Emilie. "Etude de la protéolyse protéasome-dépendante et de l'apoptose mitochondriale pendant l'atrophie et la récupération musculaire : rôle du curcumin." Clermont-Ferrand 1, 2009. http://www.theses.fr/2009CLF1MM02.
Uncontrolled and sustained muscle wasting observed in various catabolic situations (e. G. Aging, cancers, AIDS) may reduce the response to therapies and the efficiency of immune system, thus increasing morbidity and mortality. The subsequent weakness impairs human movement and ultimately can lead bed-rest, which is a worsening factor of muscle atrophy. Proteolytic and apoptotic pathways play a crucial role in the establishment of muscle atrophy. However, their respective role during recovery periods is not clearly defined. The purpose of my Ph. D. Thesis was to better characterize these mechanisms during muscle loss and the recovery following immobilization. Adult rats were subjected to unilateral hindlimb casting for 8 days and allowed to recover up to 40 days. The controlateral leg served as control in all experiments. We showed that the mitochondria-associated apoptotic pathway was up-regulated concomitantly to the ubiquitin(ub)-proteasome-dependent system during immobilization induced-muscle atrophy. We also demonstrate that these pathways are sequentially normalized during skeletal muscle recovery. Indeed, ub-proteasome-dependent proteolysis is normalized when muscle atrophy stabilized whereas the mitochondria-associated apoptotic pathway is later sequentially down-regulated and normalized when muscle mass increased. Finally, the daily administration of curcumin, which exhibit anti-oxydant and anti-inflammatory properties, speeded up muscle mass recovery by furthering the normalization of these two processes. In conclusion, my Ph. D. Thesis work demonstrated the crucial role of the mitochondria-associated apoptotic pathway during the casting induced-muscle atrophy. It further demonstrated that the ub-proteasome-dependent proteolytic and the mitochondria-associated apoptotic pathways are regulated according to different kinetics during muscle recovery. Finally, the study of the beneficial effects of curcumin indicated that nutritional strategies adapted to different stages of muscle recovery are conceivable to improve muscle mass accretion
Rodriguez-Enfedaque, Aida. "Régulation de l'apoptose mitochondriale par le facteur de survie FGF1 et l'inhibiteur de caspases zVAD-fmk." Versailles-St Quentin en Yvelines, 2009. http://www.theses.fr/2009VERS0038.
Apoptosis is a physiological cell death in multicellular organisms that is required for embryogenesis, metamorphosis, homeostasis and elimination of cells that are potentially detrimental to organism. Deregulations of apoptosis have been implicated in many pathologies. The main aim of this work is the study of the Fibroblasts Growth Factor I (FGFI) and the caspase inhibitor zVAD-fmk effects in p53-dependent apoptosis. First, we study the effect of FGF1 in p53-dependent apoptosis. As both factors have been involved in neuronal apoptosis, we realized our study in PC12 cells, a neuronal cellular model. Our results show that: (1) exogenous and endogenous (intracellular and nuclear) FGF1 inhibit p53 phosphorylation and stabilization and thus p53-dependent apoptosis, (2) FGF1 inhibits puma and noxa trans-activation induced by p53, (3) FGF1 inhibits caspases-3 cleavage and (4) the nuclear localization of endogenous FGF1 is required for its anti-apoptotic activities. Second, we study the effect of pancaspase inhibitor zVAD-fmk in mitochondrial apoptosis in rodent embryonic fibroblasts. Our results show that: (1) zVAD-fmk increases p53- and TNF-dependent apoptosis, (2) this acceleration of apoptosis by zVAD-fmk involved mitochondrial events (3) Bax and/or Bak are required for p53- and TNF-dependent apoptosis and for zVAD-fmk induced apoptosis acceleration, (4) zVAD-fmk inhibits caspases-3/7 activity and (5) surprisingly, zVAD-fmk increases caspases-9 cleavage and activity and does not seems to inhibit caspases-8
Ruby, Vincent. "Étude des évènements mitochondriaux impliqués dans le contrôle de l'apoptose par rbf1, l'homologue de drosophile du gène suppresseur de tumeur rb." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLV039/document.
The gene rb is the first tumor suppressor discovered in humans. Its prevents the appearance of tumors by regulating negatively the cell cycle. The role of pRb in apoptosis is more complex and the molecular mechanisms triggered by this transcription factor are not completely elucidated. There is a rb homologue in drosophila: rbf1. I participated in the characterization of mitochondrial events induced during activation of apoptosis by Rbf1 in a proliferating tissue of this model organism, the wing disc. In this apoptosis pathway, the Debcl protein, the only drosophila pro-apoptotic member of the Bcl-2 family, is activated and induces recruitment and oligomerization of Drp1, the main effector of mitochondrial fission. This triggers the mitochondrial fragmentation and the accumulation of mitochondrial reactive oxygen species (ROS). Both events participate to the transmission of the apoptotic signal. I have also been able to highlight the implication of factors involved in maintaining mitochondrial quality control which ensures the integrity of the mitochondria and, if necessary, triggers the degradation of damaged elements by mitophagy. Finally, I have contributed to the study of the links between translation and apoptosis induced by Rbf1. In this study, we show that the Poly-A Binding Protein (PABP) can suppress the Rbf1-induced notch phenotype in adults while cell death induced during larval stage was not inhibited but increased. These results prompted us to study the compensation mechanisms induced by the translational apparatus, which allowed us to show that a mRNA translation-related mechanism could counteract the loss of tissue resulting from Rbf1-induced apoptosis independently of apoptosis inhibition
Vijey, Jeyaraju Danny. "La protéase rhomboide PARL, nouveau contrôleur de l'apoptose et de la régulation de la morphologie mitochondriale : découverte des mécanismes moléculaires reponsables de son activité." Master's thesis, Université Laval, 2007. http://hdl.handle.net/20.500.11794/18824.
Gourdier, Isabelle. "Exploration de la résistance à l'oxaliplatine dans les cancers colorectaux : implication de la voie apoptotique mitochondriale." Montpellier 1, 2002. http://www.theses.fr/2002MON13520.
Tumor resistance to chemotherapy limits considerably the efficacy of colorectal cancer treatment. The aim of this thesis was to identify major cellular mechanisms leading to oxaliplatin resistance of colorectal cancers. For this purpose, we developed cellular models to study resistance, submitting several human colorectal cell lines to increasing concentrations of oxaliplatin. In this study, oxaliplatin resistance was found to be associated with a mitochondrial apoptosis defect, first in the HCT116 cellular model and then in a second cellular model: SW620. Indeed, oxaliplatin resistance was found to be associated with functional alterations in the mitochondrial apoptotic pathway (cross-resistance to apoptosis inducers acting directly on the mitochondria). In some cases, apoptosis alterations were found to be associated with a dysregulation of the pro-apoptotic protein Bax at several levels: genetic (Bax mutation), transcriptional (over-expression of Bax transcripts) and/or proteomic ( dawn-expression or complete loss of expression of Bax protein). Identification of these alterations in the mitochondrial apoptotic pathway in relation to acquisition of oxaliplatin resistance opens new clinical horizons among which are:(i) the development of a method to predict oxaliplatin resistance, based on the identification of tumor markers of mitochondrial apoptosis defects, and (ii) the conception of a therapeutic strategy designed to increase oxaliplatin efficacy by addition of a substance able to modulate phenomena of mitochondria-mediated apoptosis resistance
Fages, Mélanie. "Etude des interactions fonctionnelles entre les protéines de la famille Bcl-2 et les protéines PINK1 et BNIP3 dans la balance mitophagie/apoptose chez la drosophile." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASL160.
Apoptosis is a programmed cell death, allowing the physiological elimination of cells during development and that of damaged cells in multicellular organisms. This sophisticated process is associated with modifications at the level of the mitochondrial membranes involving, among others, numerous actors controlling the mitochondrial network (fusion, fission) or mitochondrial quality control (mitophagy). Several links exist between these processes. Certain members of the Bcl-2 family (B cell Lymphoma 2), identified as significant players in apoptosis, can modulate mitochondrial fission and fusion. In addition, mitophagy regulators necessary for maintaining mitochondrial integrity, such as PINK1 (PTEN Induces Kinase 1) and BNIP3 (BCL2 interacting protein 3), can modulate the apoptotic activity of specific proteins of the Bcl-2 family (BAX, BAK,…). However, the relationship between mitophagy and apoptosis remains complex. PINK1 ability to protect against apoptosis is challenged in some tissues. For its part, BNIP3 has a dual function: pro-apoptosis and pro-mitophagy.In the Drosophila model, our results show a positive regulatory role of PINK1 and a negative one for BNIP3 in apoptosis induced by rbf1 (the homolog of the retinoblastoma susceptibility gene). This apoptotic process accompanies mitophagy, which seems, in the case of RBF-1, independent of the PINK1 protein. This observation reinforces the idea of a close link between apoptosis and mitophagy and prompts us to question the role of PINK1 in this process. This project should make it possible to better understand the consequences of PINK1 deregulation according to the tissue types, neuronal or subject to renewal
Tarze, Agathe. "Recherche de nouveaux régulateurs de la phase mitochondriale de l'apoptose : approche génétique chez la levure : approche pharmacologique in cellulo : approche biochimique sur mitochondries isolées." Versailles-St Quentin en Yvelines, 2005. http://www.theses.fr/2005VERS0044.
Apoptosis is a key event for the organism intergrity throughout life. This process is frequently implied in human diseases. Understanding of the mechanisms involved in apoptosis control and characterization of new regulators are essential for development of therapeutic strategies. The objectives of my thesis deal with identification of regulators of the mitochondrial step of apoptosis. Three research orientations have been explored: (i) Study of Bax cytotoxicity in yeast model. Surexpression of the pro-apoptotic protein Bax induces cell death and itochondrial membranes permeabilization. This genetic approach in yeast highlighted the involvment of autophagy pathway in Bax’s death. (ii) Identification of nelfinavir (NFV) cellular target. This protease inhibitor of the Human Immunodeficiency Virus also presents an antiapoptotic effect, whose regulation can be a key role in apoptosis control in HIV syndrome. The biochemical and in cellulo approach we developed lead to identification of the Adenine Nucleotide Translocator (ANT), one of the components of permeability transition pore, as a target of NFV. (iii) investigation of proapoptotic function of glyceraldehyde 3 phosphate deshydrogenase (GAPDH). GAPDH is a well known protein, involved into glycolysis, but can also play a role into apoptosis. In this context, we have shown that an increase in the mitochondrial GAPDH induces the activation of the mitochondrial permeability transition, through its interaction with the porine VDAC. Using different but complementary approaches during this work allowed us to characterize one exogenous (NFV) and two endogenous (Bax, GAPDH) regulators of mitochondrial step of cell death
Talha, Samy. "Fonction endocrine cardiaque : origine de l'augmentation plasmatique du brain natriuretic peptide (BNP) après transplantation cardiaque et effets protecteurs du BNP sur la fonction mitochondriale du muscle squelettique après ischémie-reperfusion." Strasbourg, 2009. http://www.theses.fr/2009STRA3492.
Renault, Thibaud. "Régulations de la protéine proapoptotique Bax : rôle des kinases Akt et GSK-3β et de la protéine antiapoptotique Bcl-xL". Thesis, Bordeaux 2, 2010. http://www.theses.fr/2010BOR21794/document.
Proapoptotic protein Bax plays a major role during apoptosis intrinsic pathway. Bax promotes cell death by inducing the release of apoptogenic factors from mitochondria to cytosol. Bax activation is a key step of its function which involves a change from a globular, cytosolic and inactive conformation to an active mitochondrial, membrane inserted conformation. Bax activation substeps are rather well known, however their regulation remains to be characterized.This work focuses on the study of the regulation of Bax activation by kinases Akt and GSK-3β and by antiapoptotic protein Bcl-xL . Human Bax regulations have been studied by expressing the protein in yeast Saccharomyces cerevisiae which represents a simplified paradigm for the understanding of the individual components of Bax activation mecha- nisms.Our data suggest that there are two independently regulated steps during Bax activation. We showed that GSK-3β expression led to Bax addressing to mitochondria but was not sufficent to promote a complete activation and mitochondrial outer membrane premeabilization. Further conformational changes are required to promote Bax full activation and the release of mitochondrial apoptotic factors. Protein kinase Akt is involved in Bax activation control through the phosphorylation of serine 184 and contributes to apoptosis inhibition. We observed that either a phosphomimetic mutation of serine 184 or coexpression of Akt, in the absence of antiapoptotic partners, were responsible of Bax conformational change into an active form. By itself Akt did not inhibit Bax but appeared more likely to control its conformational change. Thus, implication of antiapoptotic proteins seems to be critical in a model of Bax inhibition by Akt.Furthermore, we tried to understand the molecular mechanisms of antiapoptotic protein Bcl-xL inhibition on Bax. We determined that Bcl-xL could increase Bax mitochondrial localization while leading to its inhibition suggesting that Bcl-xL controled Bax late activation steps. Bax inhibition was dependent on a stable interaction with Bcl-xL . Conversely, a variant of Bcl-xL having a transitory interaction with Bax (Bcl-xL ∆C) was able to promote Bax activation. This supports a model of Bax indirect activation following the rupture of interaction with Bcl-xL in which BH3-only proteins like Bad would play an important role
Baidi, Zineb. "Conséquences de l'ischémie/reperfusion sur le pore de transition de perméabilité mitochondrial." Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00721775.
Plin, Catherine Morin Didier. "Implication du pore géant mitochondrial dans l'évolution des fonctions mitochondriales et cellulaires au cours d'une ischémie-reperfusion hépatique." Créteil : Université de Paris-Val-de-Marne, 2004. http://doxa.scd.univ-paris12.fr:80/theses/th0214332.pdf.
Menardo, Julien. "Effets des dommages de l'ADN et du stress oxydant sur la dégénérescence des structures neuroépithéliales de la cochlée lors de l'intoxication au cisplatine et au cours du vieillissement." Thesis, Montpellier 1, 2013. http://www.theses.fr/2013MON1T012.
Our modern society is confronted with a dramatic increase in the number of patients suffering from presbycusis or age related hearing loss. Besides aging, presbycusis prevalence increases with exposition to loud noise (concerts, Walkman, work environment …) and ototoxic drugs (cisplatin, aminoglycosides …). It was reported that the early onset of some aging related diseases (Alzheimer, dementia, Parkinson …) are linked mechanistically to DNA damage, oxidative stress and inflammation. However, the role of DNA damages in cochlear cells degeneration is totally unknown and only few studies have investigated the implication of oxidative stress in presbycusis.The first goal of this study consisted in clarifying the role of DNA damage in cochlear cell degeneration. For this purpose, we used molecular and cellular biology approaches to identify the activation of DNA damage response pathways in cisplatin (CDDP) treated 3 days postnatal mouse cochlear explants in culture. Indeed, the cytotoxicity of CDDP arises from its capacity to directly damage DNA. It is also well known that one of the major dose limiting side effects of CDDP is its ototoxicity. Finally, we investigated the role of p53, a key effector of the DNA damage response pathway, in vivo by treating p53 knockout mice with CDDP. Our results show that CDDP induces double strand breaks leading to the activation of ATM-/DNA PK¬ Chk2 p53 pathway, βH2AX and 53BP1 foci formation and, in fine, apoptotic cell death. Inner hair cells, which are more resistant to CDDP treatment than outer hair cells, show a less intense signaling and fewer double strand breaks. This phenomenon could explain their weaker sensitivity to CDDP treatment. In vivo, p53 deletion prevents hearing loss and outer hair cells degeneration induced bay intraperitoneal injection of CDDP.The second goal consisted in studying the deleterious effects of aging on hearing and the molecular mechanisms involved in this pathology. Here, we studied the mechanism of presbycusis using the senescence-accelerated mouse prone 8 (SAMP8) which is a useful model to probe the effects of aging on biological processes. Based on complementary approaches combining functional, morphological, biochemistry, cellular and molecular biology, we found that the SAMP8 strain displays premature hearing loss and cochlear degeneration recapitulating the processes observed in human presbycusis (i.e. strial, sensory and neural degeneration). The molecular mechanisms associated with premature presbycusis in SAMP8 mice involve oxidative stress, mitochondrial dysfunction, chronic inflammation, autophagic stress and DNA damages. Molecular mechanisms leading to cochlear cells loss represent therapeutic targets of interest to explore in the future in order to prevent hearing impairments due to loud sound or ototoxic drugs exposure and due to aging
Clavier, Amandine. "Caractérisation des événements moléculaires et cellulaires de l’apoptose induite par rbf1, l'homologue de drosophile du gène suppresseur de tumeur rb." Thesis, Versailles-St Quentin en Yvelines, 2015. http://www.theses.fr/2015VERS025V/document.
The inactivation of the retinoblastoma susceptibility gene (rb) is a preliminary step in the development of many cancers. Consistent with its role of tumor suppressor, pRb inhibits cell proliferation. The role of pRb in apoptosis control is more complex and the molecular mechanisms underlying these functions are poorly described.rbf1 is the rb Drosophila homologue. During my PhD, I characterized the apoptosis pathway induced by Rbf1 in a proliferative tissue. I showed that Rbf1 cooperates with the dE2F2 transcription factor and with the dREAM complex to stimulate the transcription of how gene coding for a RNA binding protein able to induce the degradation of diap1 caspase inhibitor transcripts. Furthermore, Rbf1/dE2F2 proteins repress the transcription of buffy (anti-apoptotic gene of Bcl-2 family) and thus trigger a mitochondrial death pathway dependent of debcl (pro-apoptotic gene of Bcl-2 family). A mitochondrial fragmentation dependent of the Drp1 pro-fission protein promotes the accumulation of reactive oxygen species, which in turn causes JNK pathway activation, leading ultimately to apoptosis. This work clarifies the mechanism of action of Bcl-2 proteins in drosophila. It brings new data about Rbf1 pro-apoptotic function and should provide a better understanding of pRb tumor suppressor activity. Finally, I showed that Rbf1-induced apoptosis leads to compensatory proliferation and defined for the first time specific actors of the JNK pathway involved in this proliferation
Lehri-Boufala, Sonia. "Les Glycosaminoglycannes : nouveaux régulateurs de l’agrégation de l’α-synucléine et de l’apoptose dans un modèle cellulaire de la maladie de Parkinson". Thesis, Paris Est, 2011. http://www.theses.fr/2011PEST0091.
Pas de résumé anglais
Plin, Catherine. "Implication du pore géant mitochondrial dans l'évolution des fonctions mitochondriales et cellulaires au cours d'une ischémie-reperfusion hépatique." Paris 12, 2004. https://athena.u-pec.fr/primo-explore/search?query=any,exact,990002140970204611&vid=upec.
Liver transplantation is the last resort treatment for end-stage liver diseases. But the cold ischemia followed by the warm reoxygenation required by the surgery can cause damages to mitochondria. This organelle could be involved in hepatocyte cell death since opening of the permeability transition pore (PTP) can lead to necrosis and apoptosis. The purpose of this work was to study the involvement of PTP in ischemia-reperfusion damages and to determine if PTP represents a relevant pharmacologic target to protect liver during these episodes. Results show that PTP opening occured during reperfusion and that it was correlated with mitochondrial and cellular damages. Direct or indirect PTP inhibition by cyclosporine A or resveratrol, respectively, protected partially mitochondria, limited apoptosis in a concentration-dependent manner, but had no effect on necrosis
Didier, Christine. "Thioredoxine et régulation redox : conséquences sur l'adaptation cellulaire au stress oxydant." Université Joseph Fourier (Grenoble), 2001. http://www.theses.fr/2001GRE10049.
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.
Mayola, Eléonore. "Etudes des mécanismes de mort cellulaire et résistance des cellules cancéreuses pour le développement de nouvelles approches thérapeutiques : modèle du mélanome." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T012/document.
Apoptosis is a programmed cell death process necessary for tissue homeostasis duringdevelopment. Cancer cells acquire the capacity to evade apoptosis. Restoring tumor cellsability to die is a therapeutic strategy against cancer. It is therefore important to identify newtherapeutic targets within the apoptotic signaling and to test new molecules.Mitochondrion being a central integrator of cell death signals and a key player inapoptosis execution, it is a target of choice to develop new anticancer therapies. ANT(Adenine Nucleotide Translocase) is the main protein of the inner mitochondrial membrane. Itpresents a ADP/ATP transporter function in physiological conditions and acquire a lethal poreactivity upon apoptotic stimulus. It is thus interesting to inhibit the transporter function and- 6 -activate ANT pore function in order to induce apoptosis. There are four isoforms: ANT1, 2, 3and 4. We studied the role of the recently discovered ANT4 in apoptotic signaling. Our studyemphasize ANT4 anti-apoptotic role in cancer cells and ANT potential as an anticancertherapeutic target.Increase in anti-apoptotic proteins, adaptation to cellular stress and activation ofsurvival pathways are the main mechanisms responsible for chemoresistance. Using cellularmodels we studied the ability of two molecules: Withaferin A (WFA) and Plumbagin (PBG)to stimulate apoptosis and determined the molecular mechanisms involved. We showed WFAcapacity to specifically induce the mitochondrial pathway of apoptosis in melanoma cellsthrough reactive oxygen species (ROS) generation leading to mitochondrial pathwayactivation and the decrease in anti-apoptotic protein Bcl-2 expression level. However, PBG isresponsible for apoptosis and necrosis induction in melanoma cells. In both cases PBG actsthrough an increase in ROS following endoplasmic reticulum stress. WFA and PBG are thustwo pro-oxidant molecules able to induce the death of melanoma cells by taking advantage oftheir vulnerability to oxidative stress.Our work took part in the demonstration of a potential anticancer target and two agentsable to induce cell death in a context of chemoresistance
Wagner, Corinna [Verfasser], and Karsten [Akademischer Betreuer] Rippe. "Characterizing mitochondrial function and structure – Mitochondrial regulation of apoptosis and visualization of mitochondria - endoplasmic reticulum interactions / Corinna Wagner ; Betreuer: Karsten Rippe." Heidelberg : Universitätsbibliothek Heidelberg, 2014. http://d-nb.info/1180613686/34.
Sun, Mei Guo. "Mitochondrial structure during apoptosis." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3273480.
Title from first page of PDF file (viewed August 31, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 129-140).
Cipolat, Sara. "From mitochondrial morphology to apoptosis: genetic analysis of OPA1 function and regulation." Doctoral thesis, Università degli studi di Padova, 2008. http://hdl.handle.net/11577/3425557.
Ross, Katharina. "The mitochondrial protein import machinery." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2009. http://dx.doi.org/10.18452/16024.
Human mitochondria comprise about 1500 to 2000 proteins. While only 13 proteins are encoded by the mitochondrial DNA the vast majority of mitochondrial proteins is encoded in the nucleus, synthesized in the cytosol, and translocated into mitochondria by a special protein import machinery. Although many details are now known about its function several important aspects of protein import in mitochondria were not unraveled yet. To begin with, the influence of the different mitochondrial import complexes on apoptosis is not known. Further, the exact role of the protein import machineries in mitochondria in the pathogenesis of Neisseria gonorrhoeae has not been clarified yet. Moreover, the question whether factors involved in protein import are required for the maintenance of the mitochondrial morphology is still unsolved. In order to address these open issues, permanent cell lines were generated within the frame of the present thesis in which the expression of single proteins implicated in mitochondrial import can be inhibited via RNA interference (RNAi). Using these cell lines, it was investigated whether the proapoptotic proteins Bax and Bak require the import machinery in order to gain access to the outer mitochondrial membrane. The presence of both proapoptotic proteins in mitochondria is essential during apoptosis as Bax and Bak oligomerize in the outer mitochondrial membrane leading to the execution of apoptosis. In contrast to earlier publications, results presented here prove that the translocation of Bax and Bak into the outer mitochondrial membrane occurs independent of its import machineries. The second part of this thesis explores the influence of mitochondrial import proteins on the pathogenesis of Neisseria gonorrhoeae. The neisserial protein PorB translocates into the mitochondria of host cells during infection and induces apoptosis. Because of structural similarities of PorB to a certain class of proteins in the outer mitochondrial membrane, it was assumed that PorB would follow the import pathway of these endogenous proteins into the outer mitochondrial membrane. Surprisingly, it was found within the present study that PorB is not recognized by all complexes implicated in this import pathway. As a consequence, it translocates into the inner mitochondrial membrane to exert its toxic effect on the host cell. In a further project, the role of import complexes of the outer mitochondrial membrane in the maintenance of the mitochondrial morphology was investigated. Using the described cell lines, it was found that in the absence of the SAM (sorting and assembly) import device, the structure of the inner mitochondrial membrane was disrupted. Further, evidence was found that the reason for this phenotype could be an interruption of contact sites between the two mitochondrial membranes, whose preservation possibly requires the SAM complex. The results presented here allow new insights into different aspects of mitochondrial protein import. Further, with the development of the stable cell lines a new model was generated that will allow future investigations on details about mitochondrial protein import.
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.
Senille, Violette. "Etude structurale et fonctionnelle du fragment d’adressage mitochondrial de la mitogaligine." Thesis, Orléans, 2012. http://www.theses.fr/2012ORLE2058/document.
This work is about a new protein of apoptosis, mitogaligin, and more particularly about the internal fragment [31-53] responsible for its mitochondrial targeting. General aim of the project is to understand at the atomic scale its mechanism of action on mitochondrial membranes. The addressing fragment is cytotoxic by itself. That is the reason why I focused the main part of my work on this peptide. We defined its toxicity on human cells and showed that it was capable of disrupting the membrane integrity, excluding some proteins from mitochondrion. This phenomenon agrees with the release of cytochrom c, which induces apoptosis by the mitochondrial pathway. In order to better understand the mode of action of the addressing fragment and the role played by Cardiolipin, a specific lipid of mitochondrial membranes, I studied by various and complementary biophysics techniques the effect of membrane environments on the peptide structuration and the effect of the peptide on the membrane. The peptide has a very high affinity (13nM) for cardiolipin-containing membranes. It takes place parallel to the membrane, standing at the interface, without leading to a particular lipids organization. Furthermore, we highlighted that the peptide was capable of inducing a positive curvature of the membrane, what is going to interfere with numerous vital processes for the cell. Finally, to realize the structural and functional studies of the whole protein, I was involved in the first stages of mitogaligin’s production, which has proved to be very tricky either by recombinant pathway or by chemical synthesis
Medina, Luciana Paroneto. "Modulação da morte mediada por FAS em células tipo I e tipo II." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-09022012-123037/.
The death process by apoptosis can be divided into two pathways: intrinsic and extrinsic. The signaling by FAS (extrinsic) may occur in a mitochondrial independent (Type I cells) or dependent (Type II cells) manner. It is important to consider that: 1) Previous results demonstrated that sub-lethal doses of CHX were able to sensitize type I and type II cells to apoptosis and to convert type II cells into type I; 2) One of the mechanisms involved can be FAS recruitment to \"lipid rafts\"; 3) PGE2 activates PKA by increasing cAMP via EP2 and EP4, which phosphorylates of Ezrin, involved in this process; 4) PGE2 can induces apoptosis in cell lines and can to sensitize them to this process. So, we hypothesized that PGE2 could, similarly to CHX, sensitize certain cells to apoptosis and convert type II cells into type I. This effect was not observed in DO11.10 cells in which apoptosis was induced by soluble CD95L and in type I and type II cells, in which apoptosis was induced by agonist anti-FAS antibody.
Pellattiero, Anna. "Pharmacological modulation of mitochondrial dynamics: identification of a specific OPA1 inhibitor to enhance apoptotic release of cytochrome c." Doctoral thesis, Università degli studi di Padova, 2019. http://hdl.handle.net/11577/3426718.
Berson, Pascal. "Caractérisation des canaux ioniques mitochondriaux impliqués dans la signalisation apoptique." Bordeaux 2, 2008. http://www.theses.fr/2008BOR21566.
Moulis, Manon. "Implication des protéines BNIP3 et OPA1 dans la balance entre survie par autophagie-mitophagie et mort par apoptose dans les neurones." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30235.
Mitochondria are essential organelles that constantly fuse and divide. These dynamic processes are controlled by various GTPases, such as OPA1, which is involved in mitochondrial fusion. OPA1 has also an anti-apoptotic function, which is regulated by BNIP3, a pro-apoptotic member of the Bcl-2 family. Upon stresses, such as hypoxia, BNIP3 is induced and inactivates OPA1, leading to mitochondrial fragmentation and apoptosis. Besides its pro-apoptotic function, BNIP3 was recently shown to be involved in autophagy and mitophagy, a selective autophagy of mitochondria that ensures their quality control. This study aims to decipher the role of BNIP3 and its partner OPA1 in the balance between survival by autophagy-mitophagy and death by apoptosis in neurons. BNIP3 induction or overexpression was achieved, respectively, using a mimetic of hypoxia or lentiviruses, in primarily cultured neurons. Various microscopy and biochemistry approaches were used to analyse the impact of this induction/overexpression on mitochondrial morphology, autophagy-mitophagy and apoptosis. We showed that BNIP3 induction led to a sequence of events that started with mitochondrial network fragmentation, followed by pro-survival autophagic and mitophagic processes, and ended by cell death. OPA1 mutations lead to a neurodegenerative condition: Autosomal Dominant Optic Atrophy type 1 (ADOA1). ADOA1 patients suffer from optic nerve atrophy leading to blindness and various extra-ocular neurological defects. We evidenced in in vitro and in vivo ADOA1 models a lowered BNIP3 basal level. This decrease is associated in vitro with a reduction of autophagy-mitophagy that could lead to increased susceptibility to various stresses. BNIP3 thus controls, together with its partner OPA1, the fate of neurons, favoring cell survival upon moderate damages thanks to its pro-autophagic and mitophagic activity, or leading to cell death upon extensive damages. Having demonstrated that BNIP3 expression is affected in ADOA1 models, we propose a role of the protein in the etiology of the disease
Smolkova, Katarina. "Non-canonical bioenergetics of the cell." Thesis, Bordeaux 2, 2009. http://www.theses.fr/2009BOR21700/document.
Résumé non disponible
Mesquita, Lígia Garcia. "Influência da depleção e suplementação mitocondrial no processo de apoptose embrionária." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/74/74131/tde-03052010-154512/.
Studies developed with bovine zygotes submitted to a decrease of about 50% of the mitochondrial content did not present a deleterious effect on in vitro embryonic development. This model was developed by the centrifugation of zygotes after in vitro fertilization (IVF), removal of the mitochondria enriched cytoplast fraction (MECF) and posterior introduction of 20-30% ooplast (FERREIRA, 2006). Knowing that this biological model allows the development of embryos with mitochondrial depletion, the objective of this study was to evaluate the effect of the mitochondrial removal and supplementation in zygotes aiming to understand the organelle importance in the development and programmed cellular death process (PCD). Therefore, we developed a reconstruction model capable to generate mitochondrial depleted and supplemented embryos. The MECF of the centrifuged zygotes was removed from the donor\'s oocyte (depleted group-D). To prepare the supplemented group (S), a biopsy of approximately 7.1% of the cytoplasm was removed from the recipient zygote for the supplementation with MECF derived from the donor. Mitochondrial depletion caused a decrease of DNAmt amount that was replenished before 72 hours possibly due to an increase of mtTFA, BCL2 and PI3K expression and no effects in Ψmm. The technique of mitochondrial supplementation by micromanipulation showed no effect on the mitochondria DNA amount and activity estimated by mitochondrial membrane potential (Ψmm). The Ψmm increased at 168ha in consequence of an increase in COXI and mtTFA expression. Mitochondrial depletion and supplementation caused a decrease in embryonic development in the 8-cells stage, on blastocyst production and total cell number. The supplementation resulted in increased rates of fragmented nuclei possibly due to an imbalance between pro- and anti-apoptotic factors.
Vieira, Flávia Volpato. "Coronavirus Canino : Aspectos bioenergéticos relacionados com a infecção in vitro de macrófagos caninos /." Araçatuba, 2019. http://hdl.handle.net/11449/183261.
Resumo: Coronavirus são RNA vírus sentido positivo, envelopados, comumente associados a infecções brandas em aves e mamíferos. A infecção por CCoV é comum em cães jovens, principalmente em animais que vivem em canis e abrigos, associada à ocorrência de diarreia branda e autolimitante, causada pela infecção das células das vilosidades do intestino delgado. São conhecidos dois genótipos: CCoV-I e CCoV-II, o qual é subdividido em CCoV-IIa e CCoV-IIb. O CCoV-IIa, é uma variante altamente patogênica associada à doença sistêmica e acentuada linfopenia. Diferentemente de outros CCoV realiza viremia e, assim, determina a disseminação do vírus para diversos órgãos, incluindo tecidos linfóides. Nesse sentido, o envolvimento da infecção de macrófagos correlacionada à gravidade da doença e linfopenia, vem sendo sugerido. Este trabalho teve por objetivo promover a infecção de macrófagos caninos derivados de monócitos sanguíneos e avaliar a replicação viral, despolarização da membrana mitocondrial e os complexos da cadeia respiratória mitocondrial às 6, 12, 18 e 24 horas pós-infecção. A estatística descritiva incluiu média ± desvio padrão (s.d.). As médias foram comparadas através da análise de variância, ANOVA. Foi possível observar que a infecção por CCoV induziu a liberação de novas partículas virais entre 18 e 24 horas pós-infecção. Ainda, a infecção viral esteve associada à despolarização e disfunção da membrana mitocondrial, afetando o complexo III da cadeia respiratória. Desse modo, acredit... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Coronaviruses are enveloped positive-sense RNA viruses commonly associated with mild infections in birds and mammals. CCoV infection is common in young dogs, especially kennel and shelter animals, associated with the occurrence of mild, self-limiting diarrhea caused by infection of small intestinal villus cells. Two genotypes are known: CCoV-I and CCoV-II, which is subdivided into CCoV-IIa and CCoV-IIb. CCoV-IIa is a highly pathogenic variant associated with systemic disease and marked lymphopenia. Unlike other CCoV it carries viremia and thus determines the spread of the virus to various organs including lymphoid tissues. In this sense, the involvement of macrophage infection correlated with disease severity and lymphopenia has been suggested. This study aimed to promote the infection of canine macrophages derived from blood monocytes and to evaluate viral replication, mitochondrial membrane depolarization and mitochondrial respiratory chain complexes at 6, 12, 18 and 24 hours post-infection. Descriptive statistics included mean ± standard deviation (s.d.). Means were compared by analysis of variance, ANOVA. It was observed that CCoV infection induced the release of new viral particles between 18 and 24 hours after infection. Moreover, viral infection was associated with depolarization and mitochondrial membrane dysfunction, affecting respiratory chain complex III. Thus, CCoV is believed to induce mitochondrial bioenergetic failure, acting as a decoupler of the respiratory c... (Complete abstract click electronic access below)
Doutor
Pogrebniak, Alexei. "Protektive in vitro Wirkung mitochondrialer Entkoppler auf die Apoptose in Leukämiezellinien." Diss., lmu, 2003. http://nbn-resolving.de/urn:nbn:de:bvb:19-15025.
Zhao, Ming. "The lysosomal-mitochondrial axis theory of apoptosis /." Linköping : Univ, 2002. http://www.bibl.liu.se/liupubl/disp/disp2002/med747s.pdf.