From sweat to hope: The role of exercise-induced extracellular vesicles in cancer prevention and treatment.

The benefits of regular physical exercise on cancer prevention, as well as reducing fatigue, treatment side effects and recurrence, and improving quality of life and overall survival of cancer patients, are increasingly recognised. Initial studies showed that the concentration of extracellular vesicles (EVs) increases during physical activity and that EVs carry biologically active cargo. These EVs are released by blood cells, skeletal muscle and other organs involved in exercise, thus suggesting that EVs may mediate tissue crosstalk during exercise.

Smoking cessation only partially reverses cardiac metabolic and structural remodeling in mice.

Aims: Active cigarette smoking is a major risk factor for chronic obstructive pulmonary disease that remains elevated after cessation. Skeletal muscle dysfunction has been well documented after smoking, but little is known about cardiac adaptations to cigarette smoking. The underlying cellular and molecular cardiac adaptations, independent of confounding lifestyle factors, and time course of reversibility by smoking cessation remain unclear.

Diving into cancer OXPHOS - The application of metabolic control analysis to cell and tissue research.

Knowing how the oxidative phosphorylation (OXPHOS) system in cancer cells operates differently from that of normal cells would help find compounds that specifically paralyze the energy metabolism of cancer cells. The first experiments in the study of mitochondrial respiration using the metabolic control analysis (MCA) method were done with isolated liver mitochondria in the early 80s of the last century. Subsequent studies have shown that the regulation of mitochondrial respiration by ADP in isolated mitochondria differs significantly from a model of mitochondria in situ, where the contacts with components in the cytoplasm are largely preserved.

Colorectal polyps increase the glycolytic activity.

In colorectal cancer (CRC) energy metabolism research, the precancerous stage of polyp has remained rather unexplored. By now, it has been shown that CRC has not fully obtained the glycolytic phenotype proposed by O. Warburg and rather depends on mitochondrial respiration.

Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells.

Changes in dynamics of ATP γ- and β-phosphoryl turnover and metabolic flux through phosphotransfer pathways in cancer cells are still unknown. Using O phosphometabolite tagging technology, we have discovered phosphotransfer dynamics in three breast cancer cell lines: MCF7 (non-aggressive), MDA-MB-231 (aggressive), and MCF10A (control). Contrary to high intracellular ATP levels, the O labeling method revealed a decreased γ- and β-ATP turnover in both breast cancer cells, compared to control.

Wolframin deficiency is accompanied with metabolic inflexibility in rat striated muscles.

The protein wolframin is localized in the membrane of the endoplasmic reticulum (ER), influencing Ca2+ metabolism and ER interaction with mitochondria, but the exact role of the protein remains unclear. Mutations in Wfs1 gene cause autosomal recessive disorder Wolfram syndrome (WS). The first symptom of the WS is diabetes mellitus, so accurate diagnosis of the disease as WS is often delayed.

Correction: A line-broadening free real-time P pure shift NMR method for phosphometabolomic analysis.

Correction for 'A line-broadening free real-time P pure shift NMR method for phosphometabolomic analysis' by Karl Kristjan Kaup , , 2021, , 5502-5507, DOI: 10.1039/D1AN01198G.

A line-broadening free real-time P pure shift NMR method for phosphometabolomic analysis.

Phosphometabolomics by P NMR can be challenging, since overlapping multiplets of homonuclear coupled phosphorus nuclei complicate spectral analysis. Pure shift NMR allows to simplify such spectra by collapsing multiplets into singlets, but most pure shift methods require substantially elongated measurement times or cause disturbing spectral line broadening. Herein, we combine established pure shift NMR and artefact suppression techniques to record P pure shift NMR spectra without penalties in measurement time or line width.

Energy Metabolic Plasticity of Colorectal Cancer Cells as a Determinant of Tumor Growth and Metastasis.

Metabolic plasticity is the ability of the cell to adjust its metabolism to changes in environmental conditions. Increased metabolic plasticity is a defining characteristic of cancer cells, which gives them the advantage of survival and a higher proliferative capacity. Here we review some functional features of metabolic plasticity of colorectal cancer cells (CRC).

Mitochondrial Respiration in and Mutated Colorectal Tumors and Polyps.

This study aimed to characterize the ATP-synthesis by oxidative phosphorylation in colorectal cancer (CRC) and premalignant colon polyps in relation to molecular biomarkers KRAS and BRAF. This prospective study included 48 patients. Resected colorectal polyps and postoperative CRC tissue with adjacent normal tissue (control) were collected.

Adaptation of striated muscles to Wolframin deficiency in mice: Alterations in cellular bioenergetics.

Background: Wolfram syndrome (WS), caused by mutations in WFS1 gene, is a multi-targeting disease affecting multiple organ systems. Wolframin is localized in the membrane of the endoplasmic reticulum (ER), influencing Ca metabolism and ER interaction with mitochondria, but the exact role of the protein remains unclear. In this study we aimed to characterize alterations in energy metabolism in the cardiac and in the oxidative and glycolytic skeletal muscles in Wfs1-deficiency.

Altered mitochondrial metabolism in the insulin-resistant heart.

Obesity-induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA-induced lipotoxicity and uncoupling of oxidative phosphorylation.

Tubulin βII and βIII Isoforms as the Regulators of VDAC Channel Permeability in Health and Disease.

In recent decades, there have been several models describing the relationships between the cytoskeleton and the bioenergetic function of the cell. The main player in these models is the voltage-dependent anion channel (VDAC), located in the mitochondrial outer membrane. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC.

On the role of tubulin, plectin, desmin, and vimentin in the regulation of mitochondrial energy fluxes in muscle cells.

Mitochondria perform a central role in life and death of the eukaryotic cell. They are major players in the generation of macroergic compounds and function as integrated signaling pathways, including the regulation of Ca signals and apoptosis. A growing amount of evidence is demonstrating that mitochondria of muscle cells use cytoskeletal proteins (both microtubules and intermediate filaments) not only for their movement and proper cellular positioning, but also to maintain their biogenesis, morphology, function, and regulation of energy fluxes through the outer mitochondrial membrane (MOM).

Intracellular Energy-Transfer Networks and High-Resolution Respirometry: A Convenient Approach for Studying Their Function.

Compartmentalization of high-energy phosphate carriers between intracellular micro-compartments is a phenomenon that ensures efficient energy use. To connect these sites, creatine kinase (CK) and adenylate kinase (AK) energy-transfer networks, which are functionally coupled to oxidative phosphorylation (OXPHOS), could serve as important regulators of cellular energy fluxes. Here, we introduce how selective permeabilization of cellular outer membrane and high-resolution respirometry can be used to study functional coupling between CK or AK pathways and OXPHOS in different cells and tissues.

Comparative analysis of the bioenergetics of human adenocarcinoma Caco-2 cell line and postoperative tissue samples from colorectal cancer patients.

The aim of this work was to explore the key bioenergetic properties for mitochondrial respiration in the widely-used Caco-2 cell line and in human colorectal cancer (HCC) postoperational tissue samples. Oxygraphy and metabolic control analysis (MCA) were applied to estimate the function of oxidative phosphorylation in cultured Caco-2 cells and HCC tissue samples. The mitochondria of Caco-2 cells and HCC tissues displayed larger functional activity of respiratory complex (C)II compared with CI, whereas in normal colon tissue an inverse pattern in the ratio of CI to CII activity was observed.

The complexity of mitochondrial outer membrane permeability and VDAC regulation by associated proteins.

Previous studies have shown that class II β-tubulin plays a key role in the regulation of oxidative phosphorylation (OXPHOS) in some highly differentiated cells, but its role in malignant cells has remained unclear. To clarify these aspects, we compared the bioenergetic properties of HL-1 murine sarcoma cells, murine neuroblastoma cells (uN2a) and retinoic acid - differentiated N2a cells (dN2a). We examined the expression and possible co-localization of mitochondrial voltage dependent anion channel (VDAC) with hexokinase-2 (HK-2) and βII-tubulin, the role of depolymerized βII-tubuline and the effect of both proteins in the regulation of mitochondrial outer membrane (MOM) permeability.

Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently.

We conducted quantitative cellular respiration analysis on samples taken from human breast cancer (HBC) and human colorectal cancer (HCC) patients. Respiratory capacity is not lost as a result of tumor formation and even though, functionally, complex I in HCC was found to be suppressed, it was not evident on the protein level. Additionally, metabolic control analysis was used to quantify the role of components of mitochondrial interactosome.

Changes in the mitochondrial function and in the efficiency of energy transfer pathways during cardiomyocyte aging.

The role of mitochondria in alterations that take place in the muscle cell during healthy aging is a matter of debate during recent years. Most of the studies in bioenergetics have a focus on the model of isolated mitochondria, while changes in the crosstalk between working myofibrils and mitochondria in senescent cardiomyocytes have been less studied. The aim of our research was to investigate the modifications in the highly regulated ATP production and energy transfer systems in heart cells in old rat cardiomyocytes.

Bioenergetics of the aging heart and skeletal muscles: Modern concepts and controversies.

Age-related alterations in the bioenergetics of the heart and oxidative skeletal muscle tissues are of crucial influence on their performance. Until now the prevailing concept of aging was the mitochondrial theory, the increased production of reactive oxygen species, mediated by deficiency in the activity of respiratory chain complexes. However, studies with mitochondria in situ have presented results which, to some extent, disagree with previous ones, indicating that the mitochondrial theory of aging may be overestimated.

Levan Enhances Associated Growth of Bacteroides, Escherichia, Streptococcus and Faecalibacterium in Fecal Microbiota.

The role of dietary fiber in supporting healthy gut microbiota and overall well-being of the host has been revealed in several studies. Here, we show the effect of a bacterial polyfructan levan on the growth dynamics and metabolism of fecal microbiota in vitro by using isothermal microcalorimetry. Eleven fecal samples from healthy donors were incubated in phosphate-buffered defined medium with or without levan supplementation and varying presence of amino acids.

Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids.

Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by catabolism of various polysaccharides. A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed.

Deficiency of the complex I of the mitochondrial respiratory chain but improved adenylate control over succinate-dependent respiration are human gastric cancer-specific phenomena.

The purpose of study was to comparatively characterize the oxidative phosphorylation (OXPHOS) and function of respiratory chain in mitochondria in human gastric corpus mucosa undergoing transition from normal to cancer states and in human gastric cancer cell lines, MKN28 and MKN45. The tissue samples taken by endobiopsy and the cells were permeabilized by saponin treatment to assess mitochondrial function in situ by high-resolution oxygraphy. Compared to the control group of endobiopsy samples, the maximal capacity of OXPHOS in the cancer group was almost twice lower.