Expression and putative role of mitochondrial transport proteins in cancer.

Cancer cells undergo major changes in energy and biosynthetic metabolism. One of them is the Warburg effect, in which pyruvate is used for fermentation rather for oxidative phosphorylation. Another major one is their increased reliance on glutamine, which helps to replenish the pool of Krebs cycle metabolites used for other purposes, such as amino acid or lipid biosynthesis. Mitochondria are central to these alterations, as the biochemical pathways linking these processes run through these organelles. Two membranes, an outer and inner membrane, surround mitochondria, the latter being impermeable to most organic compounds. Therefore, a large number of transport proteins are needed to link the biochemical pathways of the cytosol and mitochondrial matrix. Since the transport steps are relatively slow, it is expected that many of these transport steps are altered when cells become cancerous. In this review, changes in expression and regulation of these transport proteins are discussed as well as the role of the transported substrates. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.OL was supported by Marie Curie Initial Training Networks (ITN) grant ‘MEET’ (Mitochondrial European Educational Training Project, Grant Agreement no. 317433). The work of ERSK is funded by the Medical Research Council, grant MC_U105663139

Wpływ cyfryzacji na międzynarodowe bezpieczeństwo finansowe w warunkach zrównoważonego rozwoju

The implementation of digital technologies in financial security allows you to automate and accelerate the processes of ensuring security. Electronic monitoring and analytics systems can quickly identify suspicious transactions and vulnerabilities, facilitating a prompt response to threats. That is why the topic of the current research is relevant and timely. The purpose of the study is to present the main components of the digitization process of international financial security in the context of sustainable development, with an emphasis on the formation of a comprehensive methodological approach to the analysis of the issue. The methods used in this research include the observation method to identify the main features of the digitization process of international financial security, the forecasting method to identify the main trends in the development of digital security, and the methods of analysis, synthesis, deduction, and induction to visually present the results of the research. Additionally, the graphic method is utilized to display a comprehensive methodological approach and illustrate the research results. During the course of the research, the basic components of the process of digitizing financial security were analysed, and an assessment of strengths and weaknesses was conducted. Additionally, opportunities and threats related to the process of digitizing international financial security were determined. The priority areas for the digitization of international financial security in the context of sustainable development have been identified. The main results of the study include the development of a comprehensive methodological approach to the process of digitalizing international financial security under conditions of sustainable development. The study also yields the following conclusions regarding the development of digitization: the utilization of analytical tools and artificial intelligence in financial security improves the accuracy of detecting fraud, money laundering, and other financial crimes; digital technologies facilitate access to financial services in remote and less developed regions; digital technologies enable cost optimization for ensuring financial security through automation and efficient resource utilization.Wdrożenie technologii cyfrowych w kontekście bezpieczeństwa finansowego pozwala zautomatyzować i przyspieszyć procesy zapewnienia bezpieczeństwa. Elektroniczne systemy monitorowania i analizy potrafią szybko identyfikować podejrzane transakcje i luki, ułatwiając szybką reakcję na zagrożenia. Dlatego tematyka artykułu  jest istotna i aktualna. Celem jest przedstawienie głównych elementów procesu cyfryzacji międzynarodowego bezpieczeństwa finansowego w kontekście zrównoważonego rozwoju, z naciskiem na ukształtowanie kompleksowego podejścia metodologicznego do analizy. W artykule wykorzystano następujące metody:  obserwacyjną, służącą identyfikacji głównych cech procesu cyfryzacji międzynarodowego bezpieczeństwa finansowego, metodę prognostyczną służącą identyfikacji głównych trendów rozwoju bezpieczeństwa cyfrowego oraz metody analizy, syntezy, dedukcji oraz indukcja wizualnej prezentacji wyników badań. Dodatkowo, metoda graficzna służy zobrazowaniu kompleksowego podejścia metodologicznego i zilustrowaniu wyników badań. W toku badań dokonano analizy podstawowych elementów procesu cyfryzacji bezpieczeństwa finansowego oraz dokonano oceny mocnych i słabych stron. Dodatkowo określono szanse i zagrożenia związane z procesem cyfryzacji międzynarodowego bezpieczeństwa finansowego. Zidentyfikowano priorytetowe obszary cyfryzacji międzynarodowego bezpieczeństwa finansowego w kontekście zrównoważonego rozwoju. Do głównych wyników badania należy opracowanie kompleksowego podejścia metodologicznego do procesu cyfryzacji międzynarodowego bezpieczeństwa finansowego w warunkach zrównoważonego rozwoju. Z badania wynikają także następujące wnioski dotyczące rozwoju cyfryzacji: wykorzystanie narzędzi analitycznych i sztucznej inteligencji w bezpieczeństwie finansowym poprawia skuteczność wykrywania oszustw, prania pieniędzy i innych przestępstw finansowych; technologie cyfrowe ułatwiają dostęp do usług finansowych w odległych i słabiej rozwiniętych regionach; technologie cyfrowe umożliwiają optymalizację kosztów w celu zapewnienia bezpieczeństwa finansowego poprzez automatyzację i efektywne wykorzystanie zasobów

Expression and putative role of mitochondrial transport proteins in cancer.

Cancer cells undergo major changes in energy and biosynthetic metabolism. One of them is the Warburg effect, in which pyruvate is used for fermentation rather for oxidative phosphorylation. Another major one is their increased reliance on glutamine, which helps to replenish the pool of Krebs cycle metabolites used for other purposes, such as amino acid or lipid biosynthesis. Mitochondria are central to these alterations, as the biochemical pathways linking these processes run through these organelles. Two membranes, an outer and inner membrane, surround mitochondria, the latter being impermeable to most organic compounds. Therefore, a large number of transport proteins are needed to link the biochemical pathways of the cytosol and mitochondrial matrix. Since the transport steps are relatively slow, it is expected that many of these transport steps are altered when cells become cancerous. In this review, changes in expression and regulation of these transport proteins are discussed as well as the role of the transported substrates. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.OL was supported by Marie Curie Initial Training Networks (ITN) grant ‘MEET’ (Mitochondrial European Educational Training Project, Grant Agreement no. 317433). The work of ERSK is funded by the Medical Research Council, grant MC_U105663139

Structure and Mechanical Properties of TiAlSiY Vacuum-Arc Coatings Deposited in Nitrogen Atmosphere

The effect of a negative bias potential applied to the substrate on elemental composition, structure, and mechanical properties of vacuum-arc TiAlSiY nitride coatings is investigated by different methods. It is ascertained that applying a high (up to –500 V) bias voltage leads to a selective sputtering of target as well as significant microdeformation of the coating, small-sized growth of crystallites, and their preferred orientation along the [110] direction. In this case, the coating deposited has a low hardness H = 6.95 GPa and propensity to intense wear under scratch and tribological tests. Crystallites with stoichiometric composition ~140 nm in size and [111] preferred orientation perpendicular to the surface of growth are formed at the bias potential about –200 V, and superhard (H = 49.5 GPa) and wear-resistant coatings are grown under such conditions. The mechanisms of formation of the structure of multielement coatings are discussed. It is shown that for- mation of an amorphous phase and nanocrystal [110] texture takes place at a high bias potential owing to the process of radiation-stimulated selective spraying of the target. Formation of microstrained crystallites 10 nm in size caused by the weakening of interatomic bonds is observed in the coating under such deposition condi- tions, and it leads to the decrease in coating hardness and fast destruction during tribological testing. Sub- stantial bias voltage dependence of deposited coating properties is established in our investigations

Tim50’s presequence receptor domain is essential for signal driven transport across the TIM23 complex

The Tim50 subunit of the mitochondrial TIM23 complex contains a presequence-binding domain that is essential for viability and precursor transport across the inner membrane

Strukturelle und funktionelle Analyse der Präsequenz-spezifischen mitochondriellen Translokase

Das mitochondriale Poteom der Hefe Saccharomyces cerevisiae setzt sich aus annähernd 1000 Proteinen zusammen, deren Großteil durch zytosolische Ribosomen synthetisiert wird. Daher sind spezialisierte Transportsysteme nötig, um diese Proteine an ihren Zielort zu leiten. Der TIM23-Komplex ist eine in der inneren Mitochondrienmembran liegende Proteintranslokase und verantwortlich für den Transport von Proteinen mit N-terminalem targeting signal bzw. Präsequenz. Die Erkennung dieser Präsequenz durch Einheiten der Translokase löst eine Reihe von Ereignissen aus, welche signifikante Umformungen innerhalb des Komplexes bewirken, sodass das Protein schließlich in die Matrix entlassen oder in die innere Mitochondrienmembran integriert wird. Untersuchungen der hier beteiligten Proteininteraktionen, besonders während der ersten Schritte, sind jedoch noch ungenügend für ein unstrittiges Modell des TIM23-Mechanismus. In dieser Arbeit wurden die dynamischen Veränderungen der Translokase in Abhängigkeit von Präsequenzen untersucht, wobei Interaktionspartner von Tim50, einer wichtigen TIM23-Komponente, im Mittelpunkt standen. Mit Hilfe einer cross-linking-Methode konnte eine bisher unbekannte Interaktion zwischen Tim50 und Tim21 gezeigt werden, die nach Anfügen einer Präsequenz verschwand. Ko-Immunopräzipitationsexperimente zeigen einen Zusammenhang zwischen dieser neuentdeckten Interaktion und dem Umschalten der Isoformen der Translokase. Folglich scheinen Tim21 und Tim50 hochdynamische Einheiten der TIM23-Translokase zu sein. Ein Gesamtverständnis des Proteintransports durch die Präsequenz-Translokase ist jedoch ohne strukturelle Untersuchungen nicht möglich. Daher war eines der Ziele dieser Arbeit, mit Hilfe von single particle-Elektronenmikroskopie die Struktur des TIM23-Komplexes zu lösen. Dies war jedoch nicht möglich, da das verwendete, für die Stabilität von TIM23 wichtige Detergenz, Digitonin, ein zu starkes Hintergrundsignal verursachte. Trotzdem können wir hier eine nierdrigaufgelöste Struktur eines negative stained TOM-TIM-Superkomplexes und dessen 3D-Rekonstruktion zeigen, wodurch neue Einblicke in die Organisation der Struktur der mitochondrialen Translokationsmaschinerie ermöglicht werden. Zusammenfassend leisten unsere Ergebnisse einen Beitrag zum Verständnis der Präsequenz-Import-Mechanismen und bilden eine Grundlage für weitere strukturelle Untersuchungen der TIM23-Translokase

ЕКСПЛУАТАЦІЙНІ ХАРАКТЕРИСТИКИ АДСОРБЦІЙНИХ РЕГЕНЕРАТОРІВ ТЕПЛОТИ ТА ВОЛОГИ НА ОСНОВІ КОМПОЗИТІВ «СИЛІКАГЕЛЬ – НАТРІЙ СУЛЬФАТ» ТА «СИЛІКАГЕЛЬ – НАТРІЙ АЦЕТАТ»

Operational parameters of adsorptive regenerator of low-potential heat and moisture based on composite adsorbents  «silica gel - sodium sulphate» and «silica gel  – sodium acetate» synthesized by sol – gel method were studied. Correlation of the parameters such as airflow rate, switching period, and temperatures of internal and external air, temperature efficiency factor was stated. Purposeful changing the temperature efficiency factor in rather wide ranges is shown when the switching period and airflow rate variated. Maximal values of temperature efficiency factors are stated at the airflow rates and switching over time of at most 0.22 – 0.32 m/s and 5 – 10 min., when composite «silica gel – sodium sulphate» used. Regenerators based on composites «silica gel – sodium sulphate» are stated to surpass devices based on «silica gel – sodium acetate» by at least 9 – 10 % of temperature efficiency factors. Efficiency of adsorptive regenerators is revealed to be affected by the meteorological conditions. Maximal values of temperature efficiency factor of regenerators based on composites «silica gel – sodium sulphate» are corresponded with the external air temperature of –5 – 0 °C and internal air temperature of 15 – 16 °C.  Исследованы эксплуатационные параметры адсорбционного регенератора низкопотенциального тепла и влаги на основе композитных адсорбентов «силикагель - натрий сульфат» и «силикагель - натрий ацетат», которые синтезированы золь-гель методом. Установлена корреляция таких параметров, как скорость воздушного потока, период переключения, температуры внутреннего и наружного воздуха, температурного коэффициента полезного действия. Показана целенаправленное изменение коэффициента полезного действия в достаточно широких диапазонах при изменении времени изменения направления и скорости воздушного потока. Максимальные значения температурных коэффициентов полезного действия установлено при скорости воздушного потока и времени переключения в течение времени не более 0.22 – 0.32 м / с и 5 – 10 мин. соответственно при использовании композита «силикагель - натрий сульфат».Досліджено експлуатаційні параметри адсорбційного регенератора низькопотенційного тепла та вологи на основі композитних адсорбентів  «силікагель – натрій сульфат» та «силікагель – натрій ацетат», які синтезовано  золь-гель методом. Встановлено кореляцію таких параметрів, як швидкість повітряного потоку, період перемикання, температури внутрішнього та зовнішнього повітря, температурного коефіцієнта корисної дії. Показана цілеспрямована зміна коефіцієнта корисної дії в досить широких діапазонах при зміні часу зміни напрямку та швидкості повітряного потоку. Максимальні значення температурних коефіцієнтів корисної дії встановлено при швидкості повітряного потоку і часу перемикання протягом часу не більше 0.22 – 0.32 м/с та 5 – 10 хв. відповідно при використанні композиту «силікагель – натрій сульфат

FBXL4 deficiency increases mitochondrial removal by autophagy

Abstract Pathogenic variants in FBXL4 cause a severe encephalopathic syndrome associated with mtDNA depletion and deficient oxidative phosphorylation. To gain further insight into the enigmatic pathophysiology caused by FBXL4 deficiency, we generated homozygous Fbxl4 knockout mice and found that they display a predominant perinatal lethality. Surprisingly, the few surviving animals are apparently normal until the age of 8–12 months when they gradually develop signs of mitochondrial dysfunction and weight loss. One‐year‐old Fbxl4 knockouts show a global reduction in a variety of mitochondrial proteins and mtDNA depletion, whereas lysosomal proteins are upregulated. Fibroblasts from patients with FBXL4 deficiency and human FBXL4 knockout cells also have reduced steady‐state levels of mitochondrial proteins that can be attributed to increased mitochondrial turnover. Inhibition of lysosomal function in these cells reverses the mitochondrial phenotype, whereas proteasomal inhibition has no effect. Taken together, the results we present here show that FBXL4 prevents mitochondrial removal via autophagy and that loss of FBXL4 leads to decreased mitochondrial content and mitochondrial disease

Extrinsic and intrinsic regulation of DOR/TP53INP2 expression in mice: effects of dietary fat content, tissue type and sex in adipose and muscle tissues

BACKGROUND: DOR/TP53INP2 acts both at the chromosomal level as a nuclear co-factor e.g. for the thyroid hormone receptor and at the extrachromosomal level as an organizing factor of the autophagosome. In a previous study, DOR was shown to be down-regulated in skeletal muscle of obese diabetic Zucker fa/fa rats. METHODS: To identify sites of differential DOR expression in metabolically active tissues, we measured differences in DOR expression in white adipose tissue (WAT), brown adipose tissue (BAT), skeletal muscle (SM) and heart muscle (HM) by qPCR. To assess whether DOR expression is influenced in the short term by nutritional factors, NMRI mice were fed different fat rich diets (fat diet, FD: 18% or high fat diet, HFD: 80% fat) for one week and DOR expression was compared to NMRI mice fed a control diet (normal diet, ND: 3.3% fat). Additionally, DOR expression was measured in young (45 days old) and adult (100 days old) genetically obese (DU6/DU6i) mice and compared to control (DUKs/DUKsi) animals. RESULTS: ANOVA results demonstrate a significant influence of diet, tissue type and sex on DOR expression in adipose and muscle tissues of FD and HFD mice. In SM, DOR expression was higher in HFD than in FD male mice. In WAT, DOR expression was increased compared to BAT in male FD and HFD mice. In contrast, expression levels in female mice were higher in BAT for both dietary conditions. DOR expression levels in all tissues of 100 days old genetically obese animals were mainly influenced by sex. In HM, DOR expression was higher in male than female animals. CONCLUSIONS: DOR expression varies under the influence of dietary fat content, tissue type and sex. We identified target tissues for further studies to analyze the specific function of DOR in obesity. DOR might be part of a defense mechanism against fat storage in high fat diets or obesity