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1
Mühlenbein, Nicole. "Charakterisierung der mitochondrialen TIM22-Translokase des Menschen." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-29299.
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Adam, Alexander. "Tim8 und Tim9, neue Komponenten der TIM22 Präproteintranslokase in Mitochondrien." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-31385.
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Endres, Maxi. "Funktionelle Charakterisierung des Imports des ADP-ATP-Carriers über die TIM22-Translokase der mitochondrialen Innenmembran." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963609351.
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Endres, Maxi. "Funktionelle Charakterisierung des Imports des ADP/ATP-Carriers über die TIM22-Translokase der mitochondrialen Innenmembran." Diss., lmu, 2000. http://nbn-resolving.de/urn:nbn:de:bvb:19-2204.
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Vasiljev, Andreja. "Isolation and characterisation of the intermembrane space components of the mitochondrial TIM22 protein import machinery of Neurospora crassa." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-28243.
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Mapa, Koyeli. "Conformational Dynamics of the Mitochondrial TIM23 Preprotein Translocase." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-104371.
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Glaser, Stephanie. "Structural and functional characterisation of Plasmodium falciparum Tic22." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610235.
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Mokranjac, Dejana. "Structure and function of the mitochondrial TIM23 preprotein translocase." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-23304.
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Valença, Andreia Barbosa. "Analysis of TIM2 deficiency in the mouse retina." Doctoral thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2019. http://hdl.handle.net/10400.5/18022.
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Tese de Doutoramento em Ciências Veterinárias, na especialidade de Ciências Biológicas e BiomédicasCareful control of iron availability in the retina is central to maintenance of iron homeostasis, as its imbalance is associated with oxidative stress and progress of several retinopathies, such as diabetic retinopathy. Ferritin, known for its role in iron storage and detoxification, has also been proposed as an iron-transporter and can be regarded as a potential deliverer of a considerable large amount of iron to the retina compared to transferrin, the classical ironcarrier protein. Ferritin can bind to scavenger receptor class A member 5 (Scara5) and T-cell immunoglobulin and mucin-domain 2 (TIM2) receptors and is likely endocytosed. In this study, the presence of TIM2, which remained unknown in the retina, was investigated. Although no human ortholog for mouse TIM2 has been identified, human TIM1 and mouse TIM2 have similar functions. Our results revealed for the first time the presence of TIM2 receptors in the mouse retina, mainly expressed in Müller cells, unveiling new aspects of retinal iron metabolism regarding the putative role of TIM2 in this tissue. A knockout mouse for this membrane receptor was generated in order to better understand TIM2 functions in the retina. TIM2 deficiency affected retinal iron metabolism. Iron-loaded ferritin accumulation, probably due to increased ferritin uptake mediated by Scara5, and increased iron uptake by transferrin receptor 1 (TfR1)- transferrin binding led to retinal iron overload. Consequently, increased vascular permeability and blood-retinal barrier (BRB) breakdown were observed, inducing edema of the central retina. Paracellular and transcellular transports were impaired with tight junction integrity loss and increased caveolae number. Two mechanisms seem to be involved in this process: association of iron and ferritin overload with vascular endothelial growth factor (VEGF) overexpression and oxidative stress triggered by reactive oxygen species (ROS) overproduction generated by retinal iron overload. Altogether, these results point to TIM2 as a new key player in iron homeostasis in the mouse retina, possibly modulating cellular iron levels, and a potential target for the treatment of diabetic macular edema.
RESUMO - Análise da deficiência de TIM2 na retina de murganho - A retina necessita especificamente de ferro, devido a este ser um co-factor essencial da enzima guanilato ciclase que assegura a síntese de monofosfato de guanosina cíclico, segundo mensageiro na cascata de fototransdução. Para além disso, a retina é particularmente dependente de ferro devido à contínua necessidade de síntese de membranas, para suprir a constante renovação dos segmentos externos dos fotorrecetores, que requer como co-factor este elemento. Porém, o desequilíbrio da homeostasia do ferro está associado ao dano oxidativo e ao desenvolvimento de várias situações de retinopatia, como por exemplo a retinopatia diabética. A retina é particularmente propensa a stress oxidativo e o excesso de ferro exacerba potencialmente esta situação, devido à participação do ferro na reação de Fenton, que gera a superprodução de espécies reativas de oxigénio que, por sua vez, desencadeiam stress oxidativo. Por conseguinte, a manutenção da homeostasia do ferro é crucial neste tecido. Contudo, mecanismos de regulação do ferro na retina ainda não são completamente conhecidos. A retina obtém ferro a partir da circulação sanguínea. No entanto, a barreira hemato-retiana isola a retina da circulação sanguínea, protegendo-a de potenciais estímulos nocivos. Assim, são necessários mecanismos específicos e rigorosamente regulados de absorção de ferro para atravessar esta barreira e importar a quantidade de ferro estritamente essencial para o normal funcionamento da retina. Classicamente, a transferrina foi estabelecida como a proteína transportadora de ferro na retina, sendo aceite que a transferrina sérica se liga ao seu recetor de membrana, recetor da transferrina 1, na superfície das células endoteliais e do epitélio pigmentar da retina. Após a endocitose deste complexo, o ferro é libertado no parênquima retiniano. Mais recentemente, a ferritina, considerada classicamente como uma proteína de armazenamento de ferro e destoxificação, foi também proposta como uma proteína transportadora deste elemento. A vantagem da ferritina sérica em relação à transferrina no transporte de ferro prende-se na capacidade da ferritina de incorporar ~ 4,500 átomos de ferro, ao passo que a transferrina apenas transporta 2 átomos de ferro, constituindo, assim, a ferritina uma fonte muito eficiente de ferro para os tecidos. A molécula da ferritina é composta por 24 subunidades de dois tipos: cadeia leve (L) e cadeia pesada (H) que se unem aos recetores Scara5 (scavenger receptor class A member 5) e TIM2 (T-cell immunoglobulin and mucin-domain 2), respetivamente. O nosso grupo identificou pela primeira vez a presença de recetores Scara5 na retina humana e do murganho. No entanto, até à data, a presença de recetores TIM2 na retina não foi reportada na bibliografia. O TIM2, uma proteína transmembranar do tipo 1, é um membro da família de genes portadores dos domínios mucina e imunoglobulina de células T e, para além de ser um recetor para a ferritina-H, está envolvido na regulação da resposta imunitária...
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Popov-Celeketic, Dusan. "Dynamic Regulation of Function of the Mitochondrial TIM23 Preprotein Translocase." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-81728.
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Meier, Stephan. "Untersuchungen zur Translokation und Insertion mitochondrialer Proteine über den Tim17-Tim23-Komplex." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-37366.
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Kasmati, Ali Reza. "A molecular genetic study of Tic20 and Tic22 homologues in Arabidopsis thaliana." Thesis, University of Leicester, 2010. http://hdl.handle.net/2381/10219.
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In this study Arabidopsis thaliana was used as a plant model to investigate the involvement of Tic20 and Tic22 (translocon at the inner envelope membrane of chloroplasts, 20 kD and 22 kD, respectively) in chloroplast protein import. In Arabidopsis, there are four Tic20 homologues and two Tic22 homologues, all with predicted similarity to the corresponding pea protein (psTic20 or psTic22). Phylogenetic analyses revealed two, evolutionarily conserved sub-types of both Tic20 and Tic22, termed Group 1 and Group 2 in each case. TargetP analysis was used to predict the subcellular localization of all Arabidopsis Tic20 and Tic22 proteins to the chloroplast. Moreover, the TMHMM program was used to identify the transmembrane domains of the atTic20 proteins; all atTic20 homologues have four predicted transmembrane α-helices, like psTic20. To test the TargetP predictions, envelope localization of each protein was tested by transiently expressing YFP fusions in Arabidopsis protoplasts. Furthermore, quantitative RT-PCR (and Genevestigator) revealed that all atTIC20 homologues are expressed throughout development; atTIC20-I expression was highest in photosynthetic tissues, whereas atTIC20-IV expression was strong in nonphotosynthetic tissues and seeds. Quantitative RT-PCR also revealed that atTIC22-IV expression is higher than that of atTIC22-III. To assess functional significance of the six genes in vivo, T-DNA mutants were identified. Homozygous tic20-I-1 and tic20-I-2 plants have an albino phenotype correlated with abnormal chloroplast development. To test for functional redundancy, various tic20 double and triple mutants were studied; apart from those involving tic20-I, these were all phenotypically similar to wild type. In contrast, tic20-I tic20-IV double homozygotes could not be identified, due to gametophytic and embryonic lethality. Redundancy between atTic20-I and atTic20-IV was confirmed by partial complementation of tic20-I by atTIC20-IV overexpression. Additionally, tic22-IV tic22-III double mutants had a pale phenotype in early plant development, indicating redundancy between atTic22-IV and atTic22-III and a role during early chloroplast biogenesis.
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Wolf, Ingo. "Characterization of PratA and Tic22 proteins for functions in membrane biogenesis in Synechocystis sp. PCC 6803." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-147845.
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Calado, Botelho Salomé. "Translocation of proteins into and across the bacterial and mitochondrial inner membranes." Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-83234.
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Translocons are dynamic protein complexes with the ability to respond to specific signals and to transport polypeptides between two distinct environments. The Sec-type translocons are examples of such machineries that can interconvert between a pore forming conformation that translocates proteins across the membrane, and a channel-like conformation that integrates proteins into the membrane by lateral opening. This thesis aims to identify the signals encoded in the amino acid sequence of the translocating polypeptides that trigger the translocon to release defined segments into the membrane. The selected systems are the SecYEG translocon and the TIM23 complex responsible for inserting proteins into the bacterial and the mitochondrial inner membrane, respectively. These two translocons have been challenged in vivo with designed polypeptide segments and their insertion efficiency into the membrane was measured. This allowed identification of the sequence requirements that govern SecYEG- and TIM23-mediated membrane integration. For these two systems, “biological” hydrophobicity scales have been determined, giving the contributions of each of the 20 amino acids to the overall free energy of insertion of a transmembrane segment into the membrane. A closer analysis of the mitochondrial system has made it possible to additionally investigate the process of membrane dislocation mediated by the m-AAA protease. The threshold hydrophobicity required for a transmembrane segment to remain in the mitochondrial inner membrane after TIM23-mediated integration depends on whether the segment will be further acted upon by the m-AAA protease. Finally, an experimental approach is presented to distinguish between different protein sorting pathways at the level of the TIM23 complex, i.e., conservative sorting vs. stop-transfer pathways. The results suggest a connection between the metabolic state of the cell and the import of proteins into the mitochondria.At the time of doctoral defence the following papers were unpublished and had a status as follows: Paper nr. 1: Manuscript; Paper nr. 4: Manuscript
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Günsel, Umut [Verfasser], and Dejana [Akademischer Betreuer] Mokranjac. "Functional dissection of the Tim17-Tim23 core of the mitochondrial presequence translocase / Umut Günsel ; Betreuer: Dejana Mokranjac." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1221761528/34.
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Silva, Alinne Costa. "Aparato de importação de proteínas mitocondriais em Aspergillus fumigatus: caracterização fenotípica da deleção da menor subunidade do complexo TIM23." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17131/tde-06062017-161751/.
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O câncer de ovário (OvCa) se destaca dentre as neoplasias ginecológicas por ser um dos mais letais e de difícil diagnóstico. O OvCa ocorre devido ao acúmulo de alterações celulares progressivas promovidas por mutações no genoma de uma célula que, consequentemente, alteram as complexas vias de regulação celular que respondem a fatores internos, como reprogramação genética, ou externos, como a resposta a fatores de crescimento, que juntamente com outras alterações moleculares favorecem a progressão e a metástase. Uma importante etapa da cascata metastática é a transição epitélio-mesenquimal (EMT), um processo bem orquestrado que resulta na perda do fenótipo epitelial e aquisição do fenótipo mesenquimal pelas células tumorais, que adquirem um caráter mais invasivo e migratório, além de se tornarem mais resistentes às drogas. A desregulação de fatores de transcrição como ZEB1, TWIST e SNAI1, vias de sinalização, microRNAs e fatores de crescimento incluindo EGF, TGF? e HGF podem desencadear a EMT. Após a eficiente indução da EMT com EGF na linhagem epitelial de adenocarcinoma de ovário humano Caov-3, foi realizada a análise proteômica quantitativa detalhada, baseada na análise de frações subcelulares enriquecidas em proteínas de membrana, citosol e núcleo, obtidas por centrifugação diferencial e subsequente fracionamento de proteínas por SDS-PAGE, a fim de compreender mais profundamente os mecanismos moleculares modulados pela EMT no OvCa. A partir da análise dos dados coletados em um sistema de espectrometria de massas de alta resolução acoplados a cromatografia líquida (LCMS/MS) e com o auxílio da bioinformática foram identificadas redes de interação proteína-proteína diferencialmente expressas, relacionadas principalmente com a regulação do ciclo celular e do metabolismo. A indução da EMT por EGF resultou na ativação de importantes vias de sinalização, tais como PI3K/Akt/mTOR e Ras/MAPK Erk, além da parada do ciclo celular na fase G1 regulada pelo aumento dos níveis de p21Waf1/Cip1, independentemente de p53, e diminuição de proteínas checkpoint. Através da proteômica dirigida, o monitoramento de reações múltiplas (MRM) revelou que, após a indução da EMT por EGF, o metabolismo das células Caov-3 foi alterado de uma maneira bastante peculiar. O estudo proteômico descrito permitiu a correlação entre processo da EMT induzido por EGF com o controle translacional, a regulação do ciclo celular e a alteração do metabolismo energético.Ovarian cancer (OvCa) stands out among gynecological malignancies for being one of the most lethal and difficult to diagnose. OvCa occurs due to the accumulation of progressive cell changes promoted by mutations in the cell genome which, consequently, alter the complex cellular regulation pathways that respond to internal factors, such as genetic reprogramming, or external, such as response to growth factors, which together with other molecular changes favor the progression and metastasis. An important step of the metastatic cascade is the epithelial-mesenchymal transition (EMT), a well-orchestrated process that results in the loss of epithelial phenotype and acquisition of mesenchymal phenotype by tumor cells that acquire a more invasive and migratory character, and become more resistant to drugs. Deregulation of transcription factors such as ZEB1, TWIST and SNAI1, signaling pathways, microRNAs and growth factors including EGF, TGF? and HGF can trigger EMT. After an efficient EMT induction by EGF in the epithelial cell line of human adenocarcinoma ovarian Caov-3, detailed quantitative proteomic analysis was performed based on analysis of subcellular fractions enriched in proteins from membrane, cytosol and nucleus, obtained by differential centrifugation and subsequent fractionation of proteins by SDS-PAGE, in order to understand deeply the molecular mechanisms modulated by EMT in OvCa. From the analysis of data collected in a highresolution mass spectrometry system coupled to liquid chromatography (LC-MS/MS) and with the aid of bioinformatics were identified protein-protein interaction networks differentially expressed, mainly related to regulation cell cycle and metabolism. EGF induced-EMT resulted in the activation of major signaling pathways such as PI3K/Akt/mTOR and Ras/MAPK Erk, in addition to G1 phase cell cycle arrest regulated by increased levels of p21Waf1/Cip1, regardless of p53, and reduction of checkpoint proteins. Through the targeted proteomics, multiple reaction monitoring (MRM) showed that after EGF induced-EMT, Caov-3 cells metabolism was changed in a very particular way. The proteomic study described allowed the correlation between EMT process induced by EGF with translational control, regulation of cell cycle and the change in the energy metabolism.
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Wolf, Ingo [Verfasser], and Jürgen [Akademischer Betreuer] Soll. "Characterization of PratA and Tic22 proteins for functions in membrane biogenesis in Synechocystis sp. PCC 6803 / Ingo Wolf. Betreuer: Jürgen Soll." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2012. http://d-nb.info/1025822080/34.
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Guo, Liang. "Structural and functional studies of mitochondrial small Tim proteins." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/structural-and-functional-studies-of-mitochondrial-small-tim-proteins(03dde6fd-6692-4af5-9023-b85a33803fcd).html.
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Most mitochondrial proteins are encoded by nuclear DNA, and synthesised in the cytosol, then imported into the different mitochondrial subcompartments. To reach their destination, mitochondrial inner membrane proteins require import across the outer mitochondrial membrane, and through the intermembrane space. This passage through the IMS is assisted by the small Tim proteins. This family is characterised by conserved cysteine residues arranged in a twin CX3C motif. They can form Tim9-Tim10 and Tim8-Tim13 complexes, while Tim12 appears to form part of a Tim9-Tim10-Tim12 complex that is associated with the inner membrane translocase TIM22 complex. Current models suggest that the biogenesis of small Tim proteins and their assembly into complexes is dependent on the redox states of the proteins. However, the role of the conserved cysteine residues, and the disulphide bonds formed by them, in small Tim biogenesis and complex formation is not clear. As there is no research about the structural characterisation of Tim12 and double cysteine mutants of Tim9, purification of these proteins was attempted using different methods. To investigate how cysteine mutants affect complex formation, the purified double cysteine mutants of Tim9 were studied using in vitro methods. It showed that the double cysteine mutants were partially folded, and they can form complexes with Tim10 with low affinities, suggesting disulphide bonds are important for the structures and complex formation of small Tim proteins. The effect of cysteine mutants on mitochondrial function was addressed using in vivo methods. It showed that cysteines of small Tim proteins were not equally essential for cell viability, and growth defect of the lethal cysteine mutant was caused by low level of protein. Thus, the conclusion of this study is that disulphide bond formation is highly important for correct Tim9- Tim10 complex formation, and yeast can survive with low levels of complex, but it results in instability of the individual proteins.
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Mühlenbein, Nicole [Verfasser]. "Charakterisierung der mitochondrialen TIM22-Translokase des Menschen / von Nicole Mühlenbein." 2004. http://d-nb.info/973142812/34.
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Adam, Alexander C. [Verfasser]. "Tim8 und Tim9, neue Komponenten der TIM22-Präproteintranslokase in Mitochondrien / vorgelegt von Alexander C. Adam." 2004. http://d-nb.info/974357677/34.
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Endres, Maxi [Verfasser]. "Funktionelle Charakterisierung des Imports des ADP-ATP-Carriers über die TIM22-Translokase der mitochondrialen Innenmembran / Maxi Endres." 2001. http://d-nb.info/963609351/34.
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Kumar, Abhishek. "Understanding the structural organization of the carrier translocase machinery in regulating mitochondrial biogenesis and organelle quality control." Thesis, 2020. https://etd.iisc.ac.in/handle/2005/5036.
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Mitochondria are essential eukaryotic organelles required for diverse cellular functions including, energy homeostasis, iron-sulfur cluster biogenesis, and signaling. Therefore, the maintenance of organelle quality control is critical for cell survival, and any impairment in mitochondrial function is detrimental to cells. Proper mitochondrial functioning requires accurate and efficient transport of approximately 99% of proteins from the cytosol to their precise location into the mitochondria. This protein import is performed by sophisticated protein machinery present at the outer and inner mitochondrial membranes. The outer membrane contains the TOM complex, which serves as a general entry gate for most of the mitochondrial proteins. The inner membrane harbors two distinct import machinery types, namely, the presequence translocase (TIM23 complex) and the carrier translocase (TIM22 complex). The TIM23 complex is dedicated machinery for importing proteins containing N-terminal cleavable targeting signals into the matrix and inner membrane. On the other hand, the TIM22 complex facilitates the import of polytopic inner membrane proteins having internal hydrophobic targeting sequences.
Tim22 forms the central channel of the carrier translocase with a twin pore structure. However, the role of the central channel forming Tim22 protein in modulating the assembly process of carrier translocase machinery coupled to protein import remains still elusive. In the present study, we report a novel set of conditional mutants isolated by an unbiased genetic screen from different regions of Tim22. Our genetic and biochemical analyses revealed a distinct functional role for different segments of Tim22 in the assembly of carrier translocase machinery. Further, we demonstrated that impairment in the TIM22 complex assembly process influences its translocase activity, the mitochondrial network, and the viability of cells lacking mitochondrial DNA. Overall, our results provide compelling evidence highlighting the functional significance of conserved regions of Tim22 in maintaining the TIM22 complex and mitochondrial integrity.
As the substrates of the TIM22 pathway are highly hydrophobic, these proteins' turnover requires efficiently monitored to maintain proteostasis within the organelle. Mitochondria contain several proteases that provide protein quality control in different subcompartments. Yeast mitochondrial escape 1 (Yme1) is an inner membrane AAA class of metalloprotease, which regulates protein quality control with the aid of chaperone-like and proteolytic activities. The current study highlights a novel functional cross-talk between the TIM22 pathway and Yme1. Furthermore, our genetic and biochemical analyses provide compelling evidence for the role of the TIM22 complex and Yme1 in regulating inner membrane protein quality control and mitochondrial health.
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Vasiljev, Andreja [Verfasser]. "Isolation and characterisation of the intermembrane space components of the mitochondrial TIM22 protein import machinery of Neurospora crassa / von Andreja Vasiljev." 2004. http://d-nb.info/972839267/34.
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Lytovchenko, Oleksandr. "Structural and Functional Analysis of the Mitochondrial Presequence Translocase." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-F0BD-5.
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Mapa, Koyeli [Verfasser]. "Conformational dynamics of the mitochondrial TIM23 preprotein translocase / vorgelegt von Koyeli Mapa." 2009. http://d-nb.info/996528415/34.
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Mokranjac, Dejana [Verfasser]. "Structure and function of the mitochondrial TIM23 preprotein translocase / von Dejana Mokranjac." 2004. http://d-nb.info/972016201/34.
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Ye, Han-Yu, and 葉涵瑜. "EZH2 promotes metastasis by repressing TIMP2 transcription in triple negative breast cancer cells." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/96hk22.
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碩士中國醫藥大學
癌症生物學研究所碩士班
102
Polycomb group genes (PcGs) are epigenetic effectors, essential for stem cell self-renewal 、 pluripotency and cancer malignancy. Two main Polycomb repressive complexes (PRC1, PRC2) mediate gene silencing through histone post-translational modifications. EZH2, together with SUZ12 and EED, forms the PRC2, which catalyzes trimethylation of histone H3 lysine 27 (H3K27me3). EZH2 is overexpressed widely in cancer cells. However, how EZH2 regulates metastasis in triple negative breast cancers (TNBCs) is not clear. In our current study, we found that EZH2 overexpressed in human TNBC cells. EZH2 knockdown increased the TIMP2 expression and also reduced the proteolytic activity of MMP-2 and MMP-9, thereby decreasing the invasive activity of TNBC cells. These results suggest that the transcriptional repression of the TIMP genes by EZH2 may be a major mechanism to shift the MMPs/TIMPs balance in favor of MMP activity and thus to promote ECM degradation and subsequent invasion of TNBC cells.
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Bajaj, Rakhi. "Residue level characterization of molecular interactions of intermembrane space domains governing the preprotein import into the mitochondrial matrix." Doctoral thesis, 2013. http://hdl.handle.net/11858/00-1735-0000-0023-9958-7.
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Popov-Čeleketić, Dušan [Verfasser]. "Dynamic regulation of function of the mitochondrial TIM23 preprotein translocase / von Dušan Popov-Čeleketić." 2007. http://d-nb.info/988190265/34.
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Meier, Stephan [Verfasser]. "Untersuchungen zur Translokation und Insertion mitochondrialer Proteine über den Tim17-Tim23-Komplex / Stephan Meier." 2005. http://d-nb.info/975434381/34.
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Schendzielorz, Alexander Benjamin. "Import of proteins along the presequence pathway." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-0023-3F95-8.
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Denkert, Niels. "Molecular Characterization of the Mitochondrial Presequence Translocase." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-002E-E33D-5.
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Chuang, Meng-Rong, and 莊孟蓉. "Amino acid composition of chloroplast inner membrane stop-transfer signals and import pathway of intermembrane-space protein Tic22." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/ud787a.
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碩士國立臺灣大學
分子與細胞生物學研究所
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Chloroplasts are composed of three independent membrane systems, including the outer membranes (OM), inner membranes (IM) and thylakoid membranes. These three membranes enclose three soluble areas, the intermembrane space, the stroma and the thylakoid lumen. Proteins need to be delivered to the correct compartment in order to be functional. For membrane proteins insertion into IM, two import pathways have been reported, the ‘‘stop-transfer’’ and the ‘‘post-import’’ pathways. It has been shown that the transmembrane domain (TMD) of each IM protein plays a critical role as the pathway determinant. However what features within TMD endow pathway selection is not known. Analysis of TMDs and surrounding amino acids from nine proteins of the post-import pathway and five proteins of the stop-transfer pathway, we found that there are more large amino acids in TMD of protein using the stop-transfer pathway while smaller amino acids are enriched in the post-import group. Thus, we hypothesize that one of determinants for IM insertion pathway selection is the amino acid size in TMD. We tested our hypothesis using TGD2, a protein using the stop-transfer pathway. After site-directed mutagenesis in TMDs and import assays using isolated pea chloroplasts, we found that TGD2 partly lost its ability to stop at IM after mutating a tryptophan (W) at the N terminus of its TMD into alanine (A) or glycine (G) in TMD, while mutating the W to phenylalanine (F) has no effect. These data suggest that N terminal amino acid sizes are important for TMD of chloroplast inner membrane proteins to function as a stop-transfer signal. Protein import into internal compartments of chloroplasts requires the TOC and TIC translocon complexes on the outer and inner membranes. Protein insertion into the OM only needs the TOC complex. Much less is known about how proteins are imported into the intermembrane space. For example, whether the import of Tic22, the best known intermembrane space protein, needs the TOC complex is still in debates. After enhancing the chloroplast import efficiency of Tic22 perprotein (prTic22), I performed import time course and ATP concentration experiments to characterize the import requirement of prTic22. I further performed import competition experiments using prRBCS and prTic22. My result showed that prTic22 import was competed by prRBCS, indicating that their import pathways at least partially overlap. Finally using chloroplasts isolated from translocon complex mutants, I showed that import of prTic22 was decreased in toc33 and toc75 mutant chloroplasts, was no changed in tic20 mutant chloroplasts and was increased in tic236 mutant chloroplasts. We concluded that prTic22 uses the TOC complex for crossing the OM to arrive at the intermembrance space, and its import does not require the TIC complex.
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Lin, Chia-Chie, and 林加婕. "The study of the MMPs and TIMP2 in women with breast cancer and men with oral cancer patients in Taiwan." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/02240292243422595904.
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碩士高雄醫學大學
醫學檢驗生物技術學研究所
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貳. 英文摘要 Breast cancer is one of the most common cancers in the world, including Taiwan. Previous studies have indicated that age, alcohol, and tobacco habits were related to breast cancer which involves multiple hereditary and environmental risk factors. Oral cancer in Taiwan is also one of the most common cancers especially in man. Chewing betel nuts and smoking were risk factors that might cause oral cancer. Additionally, several studies have also indicated that genetic factors were associated with the risk of breast and oral cancer. Matrix metalloproteinases (MMPs) can degrade different components of the extracellular matrix (ECM), and several studies indicated that MMPs played important roles in tumor growth, invasion and metastasis. Tissue inhibitors of metalloproteinases (TIMPs) are natural inhibitors of MMPs, and it inhibits the proteolytic activity of MMPs. Many studies indicated that single nucleotide polymorphisms (SNPs) of MMPs and TIMPs are associated with risk of breast cancer and oral cancer. We collected 283 women with breast cancer and 200 healthy people age-matched controls, and 114 men with oral cancer and 122 healthy controls. We investigated the MMP2, MMP9, and TIMP2 SNPs and risk of breast and oral cancer by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). To analysis the relationship between SNPs and prognosis factors of breast cancer and oral cancer. Second, we collected 278 women breast cancer tissue from Kaohsiung Medical University Chung-Ho Memorial Hospital and evaluated the expressions of MMP2, MMP9 and TIMP2 by Immunohistochemistry stain (IHC). Finally, we collected serum in 283 patients with breast cancer, 110 patients with oral cancer and 120 healthy controls to investigate enzyme activity by gelatin zymorgraphy. MMP9 1712C>G G carrier were more susceptible to breast cancer compared with those with the CC genotype (p=0.002). MMP9 -1562C>T/MMP9 1712C>G C/G and T/C carrier, MMP91712C>G/TIMP2 -418G>C G/G carrier had gene-gene interaction and higher risk of breast cancer compared with wild type. In total and non-TNB group, MMP2 -1306C>T T carrier had lower risk of lymph-node metastasis compared with those with the CC genotype (p=0.016；p=0.04). In premenopausal, ER-PR+ and TNB groups, MMP9 -1562C>T T carrier had lower risk of lymph-node metastasis compared with those with the CC genotype (p=0.02；p=0.02；p=0.04). In ER-PR- group, MMP9 -1562C>T T carrier had higher risk of early TNM stage compared with those with the CC genotype (p=0.05). In TNB group, MMP9 -1562C>T T carrier had higher risk of well histological differentiation compared with those with the CC genotype (p=0.04). There were no significant association between MMP2, MMP9 and TIMP2 protein expression and risk of breast cancer, including prognosis factors. MMP9 activity were higher in premenopausal, low HER2 expression and TNB group (p=0.02； p=0.04；p=0.01). MMP9 1712C>G G carrier has 3.52-fold risk of oral cancer compared with those with the CC genotype (p=0.002). In haplotype analysis, MMP-1306/-1562/1712 has significant association between oral cancer patients and controls (p=0.002)；MMP9 -1562C>T/MMP9 1712C>G C/G and T/G carrier, MMP91712C>G/TIMP2 -418G>C G/G and G/C carrier had gene-gene interaction and higher risk of oral cancer compared with wild type. TIMP2 -418G>C C carrier had lower risk of late TNM stage (p=0.02). Patients with oral cancer have higher MMP9 activity compared with controls (p<0.01)； MMP9 -1562C>T T carrier had higher MMP9 activity compared with those with the CC genotype (p=0.04)；MMP9 1712C>G G carrier had lower MMP9 activity compared with those with the CC genotype (p=0.01). Patients have higher MMP9 activity of early TNM stage compared with those in late TNM stage (p=0.002). In conclusion, our data indicated that MMP9 1712C>G G carrier were more susceptible to breast cancer and oral cancer compared with those with the CC genotype. Secondly, in gene-gene interaction analysis, MMP9 -1562C>T/MMP9 1712C>G C/G and MMP91712C>G/TIMP2 -418G>C G/G carrier had higher risk of cancers. Thirdly, MMP and TIMP SNPs in different cancer may cause different risk of cancers and prognosis factors. MMPs and TIMP2 has significant associations between SNPs and prognosis factors in breast cancer. But, only TIMP2 has significant association between SNPs and prognosis factors in oral cancer. Finally, MMP9 SNPs in oral cancer may influence MMP9 activity. MMP9 activity in different cancer may influence different prognosis.
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"Functional analysis of Tim50, a novel subunit of the TIM23 complex that links mitochondrial protein translocation across the outer and inner membranes." Thesis, 2004. http://hdl.handle.net/2237/6355.
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Yamamoto, Hayashi, and 林. 山本. "Functional analysis of Tim50, a novel subunit of the TIM23 complex that links mitochondrial protein translocation across the outer and inner membranes." Thesis, 2004. http://hdl.handle.net/2237/6355.
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Waingankar, Tejashree Pradip. "Understanding the architecture of mitochondrial presequence translocase machinery and its implications in ALS progression." Thesis, 2022. https://etd.iisc.ac.in/handle/2005/5950.
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The current thesis describes the structural organization of the presequence translocase machinery and its functional association with ALS pathogenesis. The TIM23 complex is essential for the mitochondrial biogenesis of polypeptides with N-terminus targeting sequence into the matrix and inner membrane. Hence any defects in the import machinery are known to cause mitochondrial dysfunction affecting cellular homeostasis. The importance of the presequence translocase machinery can be highlighted as its architecture, and overall import mechanisms have remained evolutionary conserved. However, because of the complex nature of a multicellular organism, the human TIM23 complex was proposed to have multiple forms distinguished by their role in housekeeping function and disease association. The findings of the current thesis provide insights into the structural dynamics of the human TIM23 machinery and how variants of an import motor complex protein differentially influence the matrix protein translocation. Additionally, the work focuses on the functional characterization of the presequence translocase machinery under a disease background, wherein the binding of mutant results in the altered translocation of a substrate leading to mitochondrial dysfunction.CSIR
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Pareek, Gautam. "Understanding the Dynamic Organization of the Presequence-Translocase in Translocation of Preproteins Across Mitochondrial Inner Membrane." Thesis, 2014. http://etd.iisc.ac.in/handle/2005/3486.
Full textAbstract:
Mitochondrion is an endosymbiotic organelle synthesizing ~1% of its proteome, while remaining ~99% of the proteins are encoded by the nuclear genome and translated on the cytosolic ribosome. Therefore active mitochondrial biogenesis requires efficient protein transport destined for the different sub-compartments. Mitochondrion contains specialized translocation machineries in the outer and in the inner membrane known as TOM40 and TIM23-complex respectively. Import of a majority of mitochondrial proteome is mediated by inner membrane presequence translocase (TIM23 complex). However, the structural organization of Tim23-complex and mechanisms of mitochondrial inner membrane protein translocation is still elusive. Therefore, the present thesis addresses above elusive questions.
Chapter 2 highlights the functional significance of different segments of Tim23 in regulating the conformational dynamics of the presequence-translocase- Tim23 is the central channel forming subunit of the presequence-translocase which recruits additional components for the assembly of the core complex. However the functional significance of different segments of Tim23 was not understood due to the lack of suitable conditional mutants. Our study has reported many conditional mutants from different segments of Tim23 which are precisely defective in the organization of the core complex and in the recruitment of the import motor component which enhances our understanding of protein translocation across mitochondrial inner membrane.
Chapter 3 highlights the functional cooperativity among mtHsp70 paralogs and orthologs using Saccharomyces cerevisiae as a model organism- mtHsp70s are implicated in a broad spectrum of functions inside the mitochondria. In case of lower eukaryotes gene duplication event has given rise to multiple copies of Hsp70s thereby presenting an opportunity of division of function among these paralogs. The mitochondria of yeast Saccharomyces cerevisiae contains three Hsp70s, including Ssc1, Ssq1 and Ssc3 (Ecm10). The Ssc1 is essential for protein translocation and de novo protein folding functions while Ssq1 is needed for the Fe/S cluster biogenesis inside the mitochondria. Although it has been proposed earlier that, Ssc1 and Ssc3 possesses overlapping functions in protein translocation as a part of import motor in the Tim23-complex. However the physiological relevance and experimental evidences in favor above hypothesis was not established clearly. Our study has reported Ssc3 as an ‘atypical chaperone’ which cannot perform the generalized chaperone functions due to the conformational plasticity associated with both the domains of Ssc3 resulting into weaker client protein affinity, altered interaction with cochaperones and dysfunctional allosteric interface. Additionally, we have also highlighted the role of Nucleotide-binding domain in determining the functional specificity among Hsp70 paralogs and orthologs.
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Pareek, Gautam. "Understanding the Dynamic Organization of the Presequence-Translocase in Translocation of Preproteins Across Mitochondrial Inner Membrane." Thesis, 2014. http://etd.iisc.ernet.in/2005/3486.
Full textAbstract:
Mitochondrion is an endosymbiotic organelle synthesizing ~1% of its proteome, while remaining ~99% of the proteins are encoded by the nuclear genome and translated on the cytosolic ribosome. Therefore active mitochondrial biogenesis requires efficient protein transport destined for the different sub-compartments. Mitochondrion contains specialized translocation machineries in the outer and in the inner membrane known as TOM40 and TIM23-complex respectively. Import of a majority of mitochondrial proteome is mediated by inner membrane presequence translocase (TIM23 complex). However, the structural organization of Tim23-complex and mechanisms of mitochondrial inner membrane protein translocation is still elusive. Therefore, the present thesis addresses above elusive questions.
Chapter 2 highlights the functional significance of different segments of Tim23 in regulating the conformational dynamics of the presequence-translocase- Tim23 is the central channel forming subunit of the presequence-translocase which recruits additional components for the assembly of the core complex. However the functional significance of different segments of Tim23 was not understood due to the lack of suitable conditional mutants. Our study has reported many conditional mutants from different segments of Tim23 which are precisely defective in the organization of the core complex and in the recruitment of the import motor component which enhances our understanding of protein translocation across mitochondrial inner membrane.
Chapter 3 highlights the functional cooperativity among mtHsp70 paralogs and orthologs using Saccharomyces cerevisiae as a model organism- mtHsp70s are implicated in a broad spectrum of functions inside the mitochondria. In case of lower eukaryotes gene duplication event has given rise to multiple copies of Hsp70s thereby presenting an opportunity of division of function among these paralogs. The mitochondria of yeast Saccharomyces cerevisiae contains three Hsp70s, including Ssc1, Ssq1 and Ssc3 (Ecm10). The Ssc1 is essential for protein translocation and de novo protein folding functions while Ssq1 is needed for the Fe/S cluster biogenesis inside the mitochondria. Although it has been proposed earlier that, Ssc1 and Ssc3 possesses overlapping functions in protein translocation as a part of import motor in the Tim23-complex. However the physiological relevance and experimental evidences in favor above hypothesis was not established clearly. Our study has reported Ssc3 as an ‘atypical chaperone’ which cannot perform the generalized chaperone functions due to the conformational plasticity associated with both the domains of Ssc3 resulting into weaker client protein affinity, altered interaction with cochaperones and dysfunctional allosteric interface. Additionally, we have also highlighted the role of Nucleotide-binding domain in determining the functional specificity among Hsp70 paralogs and orthologs.