A5063442560- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Autophagy in Disease and Therapy
- Hippo pathway signaling and YAP/TAZ
- Biochemical and Molecular Research
- Adrenal and Paraganglionic Tumors
- Cancer, Lipids, and Metabolism
- Metabolism, Diabetes, and Cancer
- Hemophilia Treatment and Research
- Telomeres, Telomerase, and Senescence
- MicroRNA in disease regulation
- Kruppel-like factors research
- Microtubule and mitosis dynamics
- Blood Coagulation and Thrombosis Mechanisms
- Retinoids in leukemia and cellular processes
- Mesenchymal stem cell research
- Neurological Disease Mechanisms and Treatments
- Porphyrin Metabolism and Disorders
- Diet and metabolism studies
- Barrier Structure and Function Studies
- Advanced Neuroimaging Techniques and Applications
- Hormonal Regulation and Hypertension
Czech Academy of Sciences, Institute of Biotechnology
2015-2025
Czech Academy of Sciences
2009-2023
Centro de Neurociências e Biologia Celular
2018
Griffith University
2011-2013
Charles University
2011
Veterinary Research Institute
2011
Czech Academy of Sciences, Institute of Physiology
2011
Amsterdam UMC Location University of Amsterdam
2005-2010
University of Amsterdam
2005-2010
Leiden University
2010
Recently, we showed that generation of tumours in syngeneic mice by cells devoid mitochondrial (mt) DNA (ρ0 cells) is linked to the acquisition host mtDNA. However, mechanism mtDNA movement between remains unresolved. To determine whether transfer involves whole mitochondria, injected B16ρ0 mouse melanoma into C57BL/6Nsu9-DsRed2 express red fluorescent protein their mitochondria. We document acquired mitochondria from animal, leading normalisation respiration. Additionally, knockdown key...
Mitochondrial complex II (CII) has been recently identified as a novel target for anti-cancer drugs. Mitochondrially targeted vitamin E succinate (MitoVES) is modified so that it preferentially localized to mitochondria, greatly enhancing its pro-apoptotic and activity. Using genetically manipulated cells, MitoVES caused apoptosis generation of reactive oxygen species (ROS) in CII-proficient malignant cells but not their CII-dysfunctional counterparts. inhibited the dehydrogenase (SDH)...
Expression of the HER2 oncogene in breast cancer is associated with resistance to treatment, and Her2 may regulate bioenergetics. Therefore, we investigated whether disruption electron transport chain (ETC) a viable strategy eliminate Her2high disease.We demonstrate that cells tumors have increased assembly respiratory supercomplexes (SCs) complex I-driven respiration vitro vivo. They are also highly sensitive MitoTam, novel mitochondrial-targeted derivative tamoxifen. Unlike tamoxifen,...
Cellular senescence is a form of cell cycle arrest that limits the proliferative potential cells, including tumour cells. However, inability immune cells to subsequently eliminate senescent from organism may lead tissue damage, inflammation, enhanced carcinogenesis and development age-related diseases. We found anticancer agent mitochondria-targeted tamoxifen (MitoTam), unlike conventional agents, kills cancer without inducing in vitro vivo. Surprisingly, it also selectively eliminates both...
Abstract Intracellular trafficking of organelles, driven by kinesin-1 stepping along microtubules, underpins essential cellular processes. In absence other proteins on the microtubule surface, performs micron-long runs. Under crowding conditions, however, motility is drastically impeded. It thus unclear how acts as an efficient transporter in intracellular environments. Here, we demonstrate that TRAK1 (Milton), adaptor protein for mitochondrial trafficking, activates and increases robustness...
Abstract Purpose: Vitamin E analogues are potent novel anticancer drugs. The purpose of this study was to elucidate the cellular target by which these agents, represented α-tocopoheryl succinate (α-TOS), suppress tumors in vivo, with focus on mitochondrial complex II (CII). Experimental Design: Chinese hamster lung fibroblasts functional, dysfunctional, and reconstituted CII were transformed using H-Ras. cells then used form xenografts immunocompromized mice, response α-TOS studied. Results:...
The transcription factor KLF2 is considered an important mediator of the anti-inflammatory and anti-thrombotic properties endothelium. absent from low-shear, atherosclerosis-prone sites vascular tree but induced by HMG-CoA reductase inhibitors (statins) in vitro. We studied KLF2-dependent induction determinants atheroprotective status endothelium to determine whether pharmacological intervention, e.g. statins, can potentially replace shear stress.Shear stress statin effects combination with...
Abstract The proapoptotic protein Noxa, a member of the BH3-only Bcl-2 family, can effectively induce apoptosis in cancer cells, although relevant regulatory pathways have been obscure. Previous studies cytotoxic effects α-tocopheryl succinate (α-TOS) on cells identified mechanism whereby α-TOS caused requiring Noxa-Bak axis. In present study, ab initio analysis revealed conserved FoxO-binding site (DBE; DAF-16 binding element) NOXA promoter, and specific affinity FoxO proteins to this DBE...
Abstract Cell growth and survival depend on a delicate balance between energy production synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CII low , serves checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their utilization by modulating DNA cell cycle progression. Depletion leads to imbalance in synthesis, evidenced recovery the de novo pyrimidine pathway unlocking arrest from...
Respiratory complex II (CII, succinate dehydrogenase, SDH) inhibition can induce cell death, but the mechanistic details need clarification. To elucidate role of reactive oxygen species (ROS) formation upon ubiquinone-binding (Qp) site blockade, we substituted CII subunit C (SDHC) residues lining Qp by site-directed mutagenesis. Cell lines carrying these mutations were characterized on bases activity and exposed to inhibitors MitoVES, thenoyltrifluoroacetone (TTFA) Atpenin A5. We found that...