A5012724614- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Acute Lymphoblastic Leukemia research
- Childhood Cancer Survivors' Quality of Life
- Photosynthetic Processes and Mechanisms
- Biochemical and Molecular Research
- Diet and metabolism studies
- RNA and protein synthesis mechanisms
- Lipid metabolism and biosynthesis
- Metabolism, Diabetes, and Cancer
- Cardiovascular Disease and Adiposity
- Fatty Acid Research and Health
- Cancer-related molecular mechanisms research
- Blood Pressure and Hypertension Studies
- Autophagy in Disease and Therapy
- Hormonal Regulation and Hypertension
- Pancreatic function and diabetes
- Cardiovascular Function and Risk Factors
- Nitric Oxide and Endothelin Effects
- Adenosine and Purinergic Signaling
Czech Academy of Sciences, Institute of Physiology
2016-2025
Czech Academy of Sciences
2015-2024
Czech Academy of Sciences, Institute of Animal Physiology and Genetics
2019
University of Liverpool
2008-2013
Charles University
2012
Macrophage inhibitory cytokine-1 (MIC-1), a divergent member of the TGF-β superfamily, is involved in control multiple cellular processes and mediates cachexia through inhibition appetite. Adipose tissue as an endocrine organ secretes proteins (adipokines) that regulate energy homeostasis other functions. This study investigated whether MIC-1 expressed adipose secretory product adipocytes. Mouse human tissues were collected from different depots. 3T3-L1 preadipocytes induced to differentiate...
Profound loss of adipose tissue is a hallmark cancer cachexia. Zinc-α2-glycoprotein (ZAG), recently identified adipokine, suggested as candidate in lipid catabolism. In the first study, eight weight-stable and 17 cachectic patients (weight ⩾5% previous 6 months) were recruited. mRNA protein expression assessed subcutaneous (SAT), morphology was examined serum ZAG concentrations quantified. second cohort, release by SAT determined 18 15 patients. The effect on lipolysis evaluated vitro....
Zinc-alpha2-glycoprotein (ZAG) is a novel adipokine, which may act locally to influence adipocyte metabolism. This study assessed the effect of increased adiposity on ZAG expression in adipose tissue human subjects. The also examined association between and adiponectin tissue, whether modulates secretion by adipocytes.Adipose (visceral subcutaneous) was collected from subjects with wide range BMIs. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were used for vitro studies. mRNA...
Cytochrome c oxidase (COX) is regulated through tissue-, development- or environment-controlled expression of subunit isoforms. The COX4 thought to optimize respiratory chain function according oxygen-controlled its isoforms COX4i1 and COX4i2. However, biochemical mechanisms regulation by the two variants are only partly understood. We created an HEK293-based knock-out cellular model devoid both (COX4i1/2 KO). Subsequent knock-in COX4i2 generated cells with exclusive respective isoform. Both...
The Acadian variant of Fanconi Syndrome refers to a specific condition characterized by generalized proximal tubular dysfunction from birth, slowly progressive chronic kidney disease and pulmonary interstitial fibrosis. This occurs only in Acadians, founder population Nova Scotia, Canada. genetic molecular basis this is unknown. We carried out whole exome genome sequencing found that nine affected individuals were homozygous for the ultra-rare non-coding chr8:96046914 T > C; rs575462405,...
The general self-rated health (SRH) question is the most common measure employed in large population surveys. This study contributes to research on concurrent validity of SRH using representative data with biomarkers from Czech Republic, a not previously used assess measure. work determines relative contribution biomedical and social characteristics an individual's assessment. Studies have already explored associations between markers physical health. However, according PubMed systematic...
Recently, the relationship of mitochondrial DNA (mtDNA) variants to metabolic risk factors for diabetes and other common diseases has begun attract increasing attention. However, progress in this area been limited because (1) phenotypic effects variation genome are difficult isolate owing confounding nuclear genome, imprinting phenomena, environmental factors; (2) few animal models have available directly investigating mtDNA on complex phenotypes vivo. Substitution different genomes same...
Zinc-α2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested potential candidate modulation of body weight. We investigated effect increased adiposity on ZAG expression adipose tissue and liver plasma levels obese ( ob/ob ) mice compared with lean siblings. The study examined pro-inflammatory cytokine tumour necrosis factor-α (TNFα) adipocytes. Zag mRNA were significantly reduced subcutaneous (fourfold) epididymal (eightfold)...
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...
Abstract Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart . Here we exploit this relationship and show CF rat influenced a locus on chromosome 2 also associated with cardiac density. Mitochondrial tryptophanyl-tRNA synthetase ( Wars2 ), encoding an L53F protein variant within ATP-binding motif, prioritized as candidate at integrating genomic data sets. WARS2(L53F) has low enzyme activity inhibition of WARS2...
Abstract While >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase γ, no phenotypes associated with POLRMT, RNA responsible for transcription of genome. Here, we characterise clinical and molecular nature POLRMT eight individuals from seven unrelated families. Patients present global developmental delay, hypotonia, short stature, speech/intellectual disability childhood; one subject displayed an indolent progressive external ophthalmoplegia...
The oxidative phosphorylation (OXPHOS) system localized in the inner mitochondrial membrane secures production of majority ATP mammalian organisms. Individual OXPHOS complexes form supramolecular assemblies termed supercomplexes. are linked not only by their function but also interdependency individual complex biogenesis or maintenance. For instance, cytochrome c oxidase (cIV) bc1 (cIII) deficiencies affect level fully assembled NADH dehydrogenase (cI) monomeric as well supercomplex forms....
The use of thiazolidinediones (TZDs) as insulin sensitizers has been shown to have side effects including increased accumulation bone marrow adipocytes (BMAds) associated with a higher fracture risk and loss. A novel TZD analog MSDC-0602K low affinity PPARγ developed reduce adverse therapy. However, the effect on phenotype mesenchymal stem cells (BM-MSCs) in relation obesity not intensively studied yet.Here, we investigated whether 8-week treatment less detrimental loss BM-MSC properties...
Mitochondrial oxidative phosphorylation (OXPHOS) generates ATP, but OXPHOS also supports biosynthesis during proliferation. In contrast, the role of quiescence, beyond ATP production, is not well understood. Using mouse models inducible deficiency in all cell types or specifically vascular endothelium that negligibly relies on OXPHOS-derived we show selectively quiescence provides stress resistance by supporting macroautophagy/autophagy. Mechanistically, constitutively low levels endogenous...
Non-shivering thermogenesis (NST) mediated by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) can be activated via the adrenergic system response to cold or diet, contributing both thermal and energy homeostasis. Other mechanisms, including metabolism of skeletal muscle, may also involved NST. However, relative contribution these dissipating pathways their adaptability remain a matter long-standing controversy.We used warm-acclimated (30 °C) mice characterize effect an up 7-day...