Our research group focuses on the role of mitochondria in physiological and pathophysiological processes of the cell and organism. Mitochondria are the main source of cellular energy, ATP, which is essential for maintaining vital cell functions. Additionally, mitochondrial metabolism also leads to the production of oxygen radicals, reactive molecules that have a negative impact on the cell functioning, i.e. irreversible damage of cellular proteins, lipids and DNA (both mitochondrial and nuclear). Such prolonged oxidative stress in extreme cases leads to cell death. Chronic, albeit relatively moderate oxidative stress accompanies number of pathophysiological disorders including neurodegenerative diseases (such as Parkinson's and Alzheimer's disease), but for example also type 2 diabetes and pulmonary hypertension, the etiology of which we study in our laboratory. In case of irreversible damage mitochondria must be removed by specific pathway of autophagy, called mitophagy. This process is crucial for mitochondrial quality control process, disruption of which is accompanied by a number of diseases such as type 2 diabetes, which is where we study the mitophagy. Moreover, mitochondria are semiautonomous organelles for they have mitochondrial DNA (mtDNA). Genetic manipulation of the mtDNA is rather complicated and yet there has not been found satisfactory method which would allow us for e.g. gene silencing or in-situ quantification of genetic mutations in mtDNA. The development of such techniques is one of out goals. Since mitochondria are rather small organelles and resolution of commonly available light and fluorescence microscopy is not sufficient to study certain aspects of their morphology, we employ special super-resolution fluorescence microscopy. The prototype of such microscope we have recently purchased for our department. We develop further methodologies of “nanoscopy” to study mitochondrial morphology and function. Finally, we study the role of mitochondrial signaling in cancer cells and cancer-specific enzymatic pathways, study of which could be essential for the development of future anticancer drugs.
Concerning applied research, we also develop novel drug carriers to transport specific anticancer drugs called photosensitizers into cancer tissues. Our findings have been patented in Industrial Property Office of the Czech Republic.
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Projects
Publications
Zelenka, J. - Dvořák, Aleš - Alán, Lukáš - Zadinová, M. - Haluzík, M. - Vítek, L.
Hyperbilirubinemia Protects against Aging-Associated Inflammation and Metabolic Deterioration
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Oxidative Medicine and Cellular Longevity. 2016, roč. 2016, 2016, článku 6190609
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IF = 4.492
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Plecitá-Hlavatá, Lydie - Tauber, Jan - Li, M. - Zhang, H. - Flockton, A. R. - Pullamsetti, S. S. - Chelladurai, P. - D´Allessandro, A. - El Kasmi, K. C. - Ježek, Petr - Stenmark, K. R.
Constitutive Reprogramming of Fibroblast Mitochondrial Metabolism in Pulmonary Hypertension
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American Journal of Respiratory Cell and Molecular Biology. 2016, roč. 55, 1, p. 47-57
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IF = 4.082
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Plecitá-Hlavatá, Lydie - Ježek, Petr
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Integration of superoxide formation and cristae morphology for mitochondrial redox signaling
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International Journal of Biochemistry and Cell Biology. 2016, roč. 80, Nov, p. 31-50
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IF = 3.905
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Plecitá-Hlavatá, Lydie - Engstová, Hana - Alán, Lukáš - Špaček, Tomáš - Dlasková, Andrea - Smolková, Katarína - Špačková, Jitka - Tauber, Jan - Strádalová, Vendula - Malínský, Jan - Lessard, M. - Bewersdorf, J. - Ježek, Petr
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Hypoxic HepG2 cell adaptation decreases ATP synthase dimers and ATP production in inflated cristae by mitofilin down-regulation concomitant to MICOS clustering
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FASEB Journal. 2016, roč. 30, 5, p. 1941-1957
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IF = 5.299
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Li, M. - Riddle, S. - Zhang, H. - D´Alessandro, A. - Flockton, A. - Serkova, N. J. - Hansen, K. C. - Moldvan, R. - McKeon, B. A. - Frid, M. - Kumar, S. - Li, H. - Liu, H. - Canovas, A. - Medrano, J. F. - Thomas, M. G. - Iloska, D. - Plecitá-Hlavatá, Lydie - Ježek, Petr - Pullamsetti, S. - Fini, M. A. - El Kasmi, K. C. - Zhang, Q. H. - Stenmark, K. R.
Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1
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Circulation. 2016, roč. 134, 15, p. 1105-1121
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IF = 17.202
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Kostiv, Uliana - Kotelnikov, Ilya - Proks, Vladimír - Šlouf, Miroslav - Kučka, Jan - Engstová, Hana - Ježek, Petr - Horák, Daniel
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RGDS- and TAT-conjugated upconversion of NaYF4:Yb3+/Er3+&SiO2 nanoparticles: in vitro human epithelioid cervix carcinoma cellular uptake, imaging, and targeting
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ACS Applied Materials and Interfaces. 2016, roč. 8, 31, p. 20422-20431
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IF = 7.145
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Bartůněk, V. - Rak, J. - Pelánková, B. - Junková, J. - Mezlíková, M. - Král, V. - Kuchař, M. - Engstová, Hana - Ježek, Petr - Šmucler, R.
Large scale preparation of up-converting YF3:YbEr nanocrystals with various sizes by solvothermal syntheses using ionic liquid bmimCl
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Journal of Fluorine Chemistry. 2016, roč. 188, Aug, p. 14-17
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IF = 2.213
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Alán, Lukáš - Špaček, Tomáš - Pajuelo-Reguera, David - Jabůrek, Martin - Ježek, Petr
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Mitochondrial nucleoid clusters protect newly synthesized mtDNA during Doxorubicin- and Ethidium Bromide-induced mitochondrial stress
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Toxicology and Applied Pharmacology. 2016, roč. 302, Jul 1, p. 31-40
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IF = 3.847
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Alán, Lukáš - Špaček, Tomáš - Ježek, Petr
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Delaunay algorithm and principal component analysis for 3D visualization of mitochondrial DNA nucleoids by Biplane FPALM/dSTORM
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European Biophysics Journal With Biophysics Letters. 2016, roč. 45, 5, p. 443-461
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IF = 1.444
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Gabrielová, E. - Křen, Vladimír - Jabůrek, Martin - Modriansky, M.
Silymarin Component 2,3-dehydrosilybin Attenuates Cardiomyocyte Damage Following Hypoxia/Reoxygenation by Limiting Oxidative Stress
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Physiological Research. 2015, Vol. 64, 1, p. 79-91
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IF = 1.618
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