National Repository of Grey Literature 51 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Functional characterization of LACE1 APTase and mitochondrial AAA proteases YME1L and AFG3L2 in mitochondrial protein homeostasis.
Tesařová, Jana ; Stibůrek, Lukáš (advisor) ; Kalous, Martin (referee) ; Pecina, Petr (referee)
Mitochondrial protein homeostasis is crucial for cellular function and integrity. It is ensured by many specific mitochondrial proteases with possible chaperone functions located across the various mitochondrial subcompartments. In the first part, we have focused on characterization of functional overlap and cooperativity of proteolytic subunits AFG3L2 and YME1L of the mitochondrial inner membrane complexes m- and i-AAA in HEK293 cells. The double AFG3L2/YME1L knockdown cells showed severe alteration in OPA1 protein processing, marked elevation in OMA1 protease and severe reduction in SPG7. Our results reveal cooperative and partly redundant involvement of AFG3L2 and YME1L in the maintenance of mitochondrial protein homeostasis and further emphasize their importance for mitochondrial and cellular function and integrity. The aim of the second part was to characterize the cellular function of LACE1 (lactation elevated 1) in mitochondrial protein homeostasis. LACE1 protein is a human homologue of yeast Afg1 (ATPase family gene 1) ATPase. We show that LACE1 is a mitochondrial integral membrane protein that exists as a part of three complexes of approximately 140, 400 and 500 kDa. We demonstrate that LACE1 mediates degradation of nuclear-encoded complex IV subunits COX4, COX5A and COX6A. Using affinity...
Protein profiling, metabolic enzymes and transmembrane signaling in the heart of spontaneously hypertensive SHR-Tg19 rat
Manakov, Dmitry ; Novotný, Jiří (advisor) ; Kuncová, Jitka (referee) ; Kalous, Martin (referee)
Cardiovascular diseases account for the majority of deaths both worldwide and in the Czech Republic. Main factors contributing heart disease development, aside age and sex, are obesity, high blood pressure and high blood cholesterol and triglyceride levels. Spontaneously hypertensive rat (SHR) was developed and used for search of genetic determinants of these traits. This commonly used rat model develops hypertension, dyslipidemia, and insulin resistance naturally which is caused by aberrant Cd36 fatty acid translocase gene. Previous studies have shown that rescue of Cd36 performed in the transgenic SHR-Tg19 strain enhances cardiac beta-adrenergic system, slightly increases heart mass and leads to higher susceptibility to arrhythmias. The present thesis had two main aims: 1) To investigate whether and how a transgenic rescue of Cd36 in SHR affects protein composition, mitochondrial function and activity of selected metabolic enzymes of the heart. 2) To study the expression and distribution of selected components of beta-adrenergic signaling system in lipid raft isolated form membranes using the TX-100 detergent. We set to compare two commonly used proteomic approaches, 2D electrophoresis with MALDI-TOF mass spectrometry and label-free LC-MS. The results did not reveal any overlap between...
Structural composition and functional properties of mitochondrial FoF1 ATP synthase on models of specific subunits deficiencies
Efimova, Iuliia ; Mráček, Tomáš (advisor) ; Kalous, Martin (referee)
Mitochondrial ATP synthase represents the final complex of oxidative phosphorylation (OXPHOS) system located in the inner mitochondrial membrane. Its primary role is to utilize mitochondrial membrane potential (Δψm) generated by respiratory chain complexes to produce energy in the form of ATP. Mammalian ATP synthase comprises of 17 different subunits organized into membranous Fo and matrix-oriented F1 domains. Defects of complex V and their manifestation have been studied on mitochondrial, cellular, tissue and organism levels using different models, including human cell lines and cell lines derived from patient tissues. In many cases mitochondrial diseases display threshold behaviour, when genetic defect is phenotypically manifested only bellow certain threshold in particular enzyme complex activity and/or content. This work was aimed at elucidation of functional consequences of ATP synthase deficiency in HEK293 cell lines with suppressed gene expression of γ, δ or ε subunits of ATP synthase central stalk. We have analysed range of clones with respective subunits knockdown and found varying decrease in assembled ATP synthase content, which was mirrored by the decrease in individual ATP synthase subunits. The only exception was subunit Fo-c, whose levels remained unchanged or even increased. ATP...
The function of p53 protein in mitochondria
Magdálková, Kateřina ; Kalous, Martin (advisor) ; Žurmanová, Jitka (referee)
Protein p53 is known as a tumor suppressor. In nucleus, p53 regulates the expression of its target genes, which are involved in cell cycle control, DNA repair and cell death. Protein p53 also has transcription-independent activities outside the nucleus. Under physiological conditions, certain amount of this protein can be found in mitochondria, where it is involved in mitochondrial genome integrity maintaining. Under stress conditions, p53 protein rapidly translocates to outer mitochondrial membrane or mitochondrial matrix, and takes a part in apoptotic or necrotic signaling pathway. Keywords: p53, mitochondria, mtDNA, apoptosis
The function of p53 protein in mitochondria
Magdálková, Kateřina ; Stibůrek, Lukáš (advisor) ; Kalous, Martin (referee)
Protein p53 is known as a tumor supressor. In nucleus, p53 regulates the expression of its target genes, which are involved in cell cycle control, DNA repair and cell death. Protein p53 also has transcription-independent activities outside the nucleus. Certain amount of this protein can be found in mitochondria, where it is involved in mitochondrial genom integrity maintaining. Under stress conditions, p53 rapidly translocates to outer mitochondrial membrane, and takes a part in apoptotic signalling pathway. Keywords: p53, mitochondria, mtDNA, apoptosis
Mitochondrial permeability transition pore and its role in cardioprotection
Ryba, Lukáš ; Kalous, Martin (advisor) ; Brabcová, Iveta (referee)
The mitochondrial permeability transition pore (MPTP) is a non-specific voltage dependent channel which is located in the inner mitochondrial membrane. High calcium concentration and oxidative stress are main inducers of MPTP opening in a tissue which is affected by ischaemia and subsequent reperfusion. Morbidity and mortality of pacients who suffer from acute myocardial infaction or cardiochirugical operation, depends on the size of ischemic- reperfusion injury (IRI). The methods of IRI attenuation are based on the inhibition of the MPTP through farmacological intervention or ischemic conditioning. This thesis summarizes the current knowledge about the MPTP structure, regulation and its role in cardioprotection. Key words: mitochondrial permeability transition pore, cardioprotection, ischemic conditioning, CsA, SAFE and RISK pathway
Reactive oxygen species and their role in myocard injury
Selingerová, Josefína ; Kalous, Martin (advisor) ; Rauchová, Hana (referee)
Cardiac tissue is very sensitive to oxygen deprivation. Ischemia and subsequent reperfusion are the source of metabolic and structural changes. They lead to irreversible tissue damage and cell death. Under this conditions the increased production of reactive oxygen species (ROS) is crucial. ROS are highly reactive molecules, which contains at least one unpaired electron. They are formed in organism as a natural by-products of aerobic metabolism. Under physiological conditions mitochondria protect cells against ROS trough antioxidants sweeper systems and ATP synthase inhibitor. However, under pathological conditions mitochondria are one of the largest sources of ROS and they are responsible for initiation of cell death. This thesis discusses the changes in cells during the ischemia and following reperfusion. How is ion homeostasis and ATP concentration affected and why the activities of individual complexes of electron-transport chain are decreased.
Mitochondria as a target for anti-cancer therapy
Monschizadeh Tehrany, Shahin ; Truksa, Jaroslav (advisor) ; Kalous, Martin (referee)
Cancer is a complex disease that is characteristic by its heterogeneity in forms and symptoms. This diversity is caused by various mutations in oncogenes and tumor suppressor genes, which then makes cancer a very unclear and indistinct target. However numerous neoplastic characteristics are linked to the functions of mitochondria. This then makes mitochondria a center of interest of cancer research. Many cancer cells show the switch to the metabolism of aerobic glycolysis witch is characteristic by the increased glucose uptake, increased activity of biosynthetic pathways and lower oxidative capacity of mitochondria. Another mitochondria-linked modification is the increased production of reactive oxygen species in cancer cells, which are a source of new mutations and enhance cell proliferation. An increased transmembrane potential on the inner mitochondrial membrane is another very common feature that also promotes cell division and directly correlates with cancer malignancy. In this context a group of antitumor drugs called mitocans was discovered, that acts on the altered mitochondria of tumor cells. The activity of mitocans is ranging from the restoration of the function of pro-apoptotic molecules to the enforced cell death caused by oxidative damage done to the mitochondria of cancer cells....
Effect of biguanides on liver cells metabolism
Švecová, Eliška ; Kalous, Martin (advisor) ; Flachs, Pavel (referee) ; Hansíková, Hana (referee)
The extract from the plant Galega officinalis containing the guanidine derivative galegin has been used in the treatment of diabetes-associated complications since middle ages. Nevertheless, the positive effects of the treatment were often overweight by the adverse side effects. Some sixty years ago guanidin was replaced by the less toxic synthetic biguanide derivatives - metformin, phenphormin and buformin, the latter two being withdrawn due to the unacceptable risk of fatal lactate acidosis. Metformin is still widely used antidiabetics and belongs to the first choice drugs in the treatment of type 2 diabetes. Phenphormin is now gaining renewed attention with regard to its antineoplastic properties. Despite its long-term clinical use the mechanism of biguanides action is not fully understood yet. At present it is generally accepted that the core of its antihyperglycemic effect lays in the inhibition of hepatic gluconeogenesis. In contrast, there is less consensus regarding the particular metabolic pathway or target that are responsible for the metformin-induced attenuation of gluconeogenesis. For a long time, a hot candidate for metformin target in the cell was AMP-activated kinase (AMPK) but the metformin effect was proved also in mice carrying the dominant negative mutation of AMPK α subunit. Quite...

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