Tricarboxylic Acid Cycle Intermediates and Individual Ageing

Biomolecules, Год журнала: 2024, Номер 14(3), С. 260 - 260

Опубликована: Фев. 22, 2024

Anti-ageing biology and medicine programmes are a focus of genetics, molecular biology, immunology, endocrinology, nutrition, therapy. This paper discusses metabolic therapies aimed at prolonging longevity and/or health. Individual components these effects postulated to be related the energy supply by tricarboxylic acid (TCA) cycle intermediates free radical production processes. article presents several theories ageing clinical descriptions top markers ageing, which define in different categories; additionally, their interactions with age-related changes diseases α-ketoglutarate (AKG) succinate SC formation metabolism pathological states explained. review describes convincingly differences mitochondrial characteristics animals, levels (high low) physiological reactivity functional systems state regulatory providing oxygen-dependent Much attention is given crucial role AKG cells amino synthesis, epigenetic regulation, cell stemness, differentiation, as well associated development conditions and, particular, cancer cells. Another goal was address issue terms individual reactivity. also demonstrated Krebs key component cellular closely various pathologies, such cancer, type 2 diabetes, cardiovascular or neurodegenerative where mTOR pathway plays role. provides postulates postischaemic phenomena an organism demonstrates dependence accelerated pathology on studies species (roundworm Caenorhabditis elegans, Drosophila, mice, humans used models). The findings suggest that this approach may useful show metabolites involved abnormalities thus induce reprogramming contributes senile phenotype degenerative diseases. compounds particularly important when considering mechanisms connected initial able initiate programmed depending intensity oxygen consumption, peculiarities, behavioural reactions.

Язык: Английский

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The flexible chain: regulation of structure and activity of ETC complexes defines rate of ATP synthesis and sites of superoxide generation

Biophysical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 25, 2025

Язык: Английский

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Complex II ambiguities—FADH2 in the electron transfer system

Journal of Biological Chemistry, Год журнала: 2023, Номер 300(1), С. 105470 - 105470

Опубликована: Ноя. 22, 2023

The prevailing notion that reduced cofactors NADH and FADH

Язык: Английский

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Magnetic-field-driven targeting of exosomes modulates immune and metabolic changes in dystrophic muscle

Nature Nanotechnology, Год журнала: 2024, Номер 19(10), С. 1532 - 1543

Опубликована: Июль 22, 2024

Abstract Exosomes are promising therapeutics for tissue repair and regeneration to induce guide appropriate immune responses in dystrophic pathologies. However, manipulating exosomes control their biodistribution targeting them vivo achieve adequate therapeutic benefits still poses a major challenge. Here we overcome this limitation by developing an externally controlled delivery system primed annexin A1 myo-exosomes (Exo myo ). Effective nanocarriers realized immobilizing the Exo onto ferromagnetic nanotubes localization of skeletal muscles systemic injection using external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate uptake from these synergistically promote beneficial muscle murine animal model Duchenne muscular dystrophy. Our findings provide insights into development exosome-based therapies diseases and, general, highlight formulation effective functional aimed at optimizing exosome biodistribution.

Язык: Английский

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Regulation of Mitochondrial Respiration by Hydrogen Sulfide

Antioxidants, Год журнала: 2023, Номер 12(8), С. 1644 - 1644

Опубликована: Авг. 20, 2023

Hydrogen sulfide (H2S), the third gasotransmitter, has positive roles in animals and plants. Mitochondria are source target of H2S regulatory hub metabolism, stress, disease. Mitochondrial bioenergetics is a vital process that produces ATP provides energy to support physiological biochemical processes. regulates mitochondrial bioenergetic functions oxidative phosphorylation. The article summarizes recent knowledge chemical biological characteristics, biosynthesis H2S, effects on tricarboxylic acid cycle respiratory chain complexes. complexes mammals have been widely studied. function now hot topic also organelles regulating plant regulation gaining more attention. This paper mainly current (TCA) chain. A study respiration plants elucidate botanical would be highly desirable.

Язык: Английский

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Acute Severe Hypoxia Decreases Mitochondrial Chain Complex II Respiration in Human Peripheral Blood Mononuclear Cells

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 705 - 705

Опубликована: Янв. 15, 2025

Peripheral blood mononuclear cells' (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury heart failure pathophysiology, but its response to acute severe hypoxia, often associated with such diseases, largely unknown humans. We therefore determined the effects of hypoxia on PBMC ROS production healthy volunteers exposed controlled oxygen reduction, achieving an inspired fraction 10.5%. also investigated potential relationships gene expression key biomarkers succinate inflammation, as inflammation share common mechanisms cardiovascular disease. Unlike global respiration, hypoxemia a spO2 ≤ 80% significantly reduced complex II (from 6.5 ± 1.2 3.1 0.5 pmol/s/106 cell, p = 0.04). Complex activity correlated positively (r 0.63, 0.02) inversely receptor SUCNR1 -0.68), alpha-subunit hypoxia-inducible factor (HIF-1α, r -0.61), chemokine ligand-9 -0.68) interferon-stimulated 15 -0.75). In conclusion, specifically impairs association succinate, HIF-1α pathway interactions human PBMCs. These results support further studies investigating whether modulation might modify inflammatory metabolic alterations observed failure.

Язык: Английский

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Mutational analysis of the role of conserved histidine residues of the SDHC subunit of Complex II

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Background: SDHC protein is a critical component of the succinate-ubiquinone oxidoreductase also known as respiratory chain Complex II. Because mutations are associated with several human diseases, detailed understanding role in II and overall cellular physiology important. In this study, we have tested functional complementation SDHC-null cells different variants proteins fused GFP at C-terminus. Specifically, determined four conserved histidines (H55, H71, H127, H134) on function mitochondrial morphology. Methods: The SDHC-deficient Chinese hamster cell line CCL16-B9 was transfected plasmid constructs expressing (SDHC, SDHC∆, SDHC-H55N, SDHC-H71N, SDHC-H127N, SDHC-H134N) either or HA-GFP Restoration by galactose selection, biochemical assays, Western blotting, assessment morphology fluorescence microscopy. Results: key findings study are: (1) C-terminus does not interfere import, orientation, function. (2) Wild type mutant SDHCs can deliver into IMS. (3) third transmembrane domain essential for (4) While H55, H71are non-essential, H127 H134 H127N H134N impair alter most detrimental effects due to mutation. (5) serve carrier delivering interest Conclusions: This advances our subunit II, morphology, physiology.

Язык: Английский

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Effects of periconceptional ethanol on mitochondrial content and oxidative stress in maternal liver and placentas from male and female fetuses in rats

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 9, 2025

Alcohol exposure during pregnancy disrupts fetal development and programs lifelong disease. We have shown, in rats, that alcohol the periconceptional period (PC:EtOH), causes placental dysfunction cardiometabolic disease offspring. The process of metabolising can cause oxidative stress damage mitochondrial DNA (mtDNA). It is unknown whether metabolism a rat model PC:EtOH impacts markers content maternal tissues. aimed to determine induced reduced mtDNA liver labyrinth junctional zone. Sprague-Dawley rats were given an ethanol liquid (12.5% v/v) or control (0%) diet for one oestrous cycle before mating embryonic day (E) 4. Maternal livers collected at E5 E20. Placentas E20 separated into zone Cyp2e1 mRNA levels with lower persisting E20, which time proteins also decreased. zone, although protein unaffected. Superoxide dismutase activity was increased there no evidence stress. present study demonstrates around conception, reduces within placenta towards end pregnancy. These prolonged deficits may disrupted metabolic processes required healthy further supports avoiding when planning KEY POINTS: Even consumed only conception it profound on developing baby. Here, we use our established investigate if immediately after 5. these parameters (E20) placenta. by 77% 40% At expression form electron transport chain reduced. had more subtle reduction content, but complexes unchanged. There response PC:EtOH. lack be result compensatory increases antioxidants.

Язык: Английский

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Heterogeneous metabolic response of endothelial cells from different vascular beds to experimental hyperglycaemia and metformin

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Abstract Endothelial cells (ECs) are highly glycolytic, with mitochondria primarily serving a signalling function. Metabolic disruptions early contributors to endothelial dysfunction, primary feature of diabetic vascular complications, such as retinopathy, impaired wound healing and cerebral small vessel disease. The degree which metabolism varies amongst different beds is unknown. Mitochondrial function was therefore characterised in human aortic, dermal, retinal ECs vitro , aiming determine whether basal influences the response susceptibility experimental hyperglycaemia (HG). Furthermore, potential metformin maintain independent glycaemic control assessed. Using Seahorse analyser, metabolic from compared under conditions, well HG treatment. differed significantly respiratory profile glycolytic For example aortic were preferentially aerobic, whereas dermal glycolytic. lowered mitochondrial network area but elicited modest effects upon at same time influencing manner that possibly conditional utilisation. Metformin inhibited enhancing glycolysis brain ECs. These data suggest EC responses influenced by profile, highlighting targeting preserve condition. A nuanced approach needed address complications health diabetes, both investigation pathophysiology prospective therapeutics. image Key points dysfunction an diabetes‐associated cardiovascular known be heterogeneous function, how this reflected not fully understood, addition their (HG) we demonstrate Their contingent results when investigating

Язык: Английский

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Apelin‐13 Alleviates Diabetes‐Associated Cognitive Decline by Reducing Oxidative Stress and Mitochondrial Dysfunction via the SIRT3/Foxo3 Pathway

Biotechnology and Applied Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

ABSTRACT The incidence of diabetes‐related cognitive dysfunction is on the rise, yet clinical interventions to prevent this condition remain limited. Apelin‐13, an endogenous peptide known for its positive inotropic and vasoactive properties, has been shown exert diverse effects across various tissues cell types. However, potential protective role in diabetes‐associated decline (DACD) remains poorly understood. To investigate this, we established a rodent diabetes model using high‐fat diet (HFD) combined with streptozotocin (STZ, intraperitoneal injection, 60 mg/kg). Cognitive function was evaluated Morris water maze Y‐maze tests. Additionally, employed range techniques, including glucose tolerance tests (IPGTT), insulin (ITT), immunofluorescence labeling, real‐time PCR, Western blot analysis, enzyme‐linked immunosorbent assays (ELISA). Our results demonstrate that apelin‐13 administration alleviated symptoms diabetic mouse model. Specifically, improved performance both In hippocampus treated mice, reduced oxidative stress by enhancing activity superoxide dismutase (SOD) catalase (CAT), while decreasing levels malondialdehyde (MDA) 4‐hydroxynonenal (4‐HNE). Furthermore, mitochondrial restoring activities COX I IV (but not II) increasing ATP production. Apelin‐13 also restored SIRT3 expression elevated NAD+/NADH ratio hippocampus. As result, facilitated deacetylation nuclear translocation Foxo3a When silenced, beneficial stress, function, impairment mice were significantly diminished, underscoring critical these processes. summary, our findings suggest mitigates DACD reducing through SIRT3/Foxo3 pathway. These highlight as promising therapeutic candidate DACD.

Язык: Английский

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