Mechanisms of Oxidative Stress in Metabolic Syndrome

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7898 - 7898

Published: April 26, 2023

Metabolic syndrome is a cluster of conditions associated with the risk diabetes mellitus type 2 and cardiovascular diseases (CVDs). closely related to obesity. Increased adiposity promotes inflammation oxidative stress, which are precursors various complications involving metabolic components, namely insulin resistance, hypertension, hyperlipidemia. An increasing number studies confirm importance stress chronic in etiology syndrome. However, few have reviewed mechanisms underlying role contributing In this review, we highlight by reactive oxygen species (ROS) increase mitochondrial dysfunction, protein damage, lipid peroxidation, impair antioxidant function Biomarkers can be used disease diagnosis evaluation severity.

Language: Английский

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The tricarboxylic acid (TCA) cycle: a malleable metabolic network to counter cellular stress

Critical Reviews in Biochemistry and Molecular Biology, Journal Year: 2023, Volume and Issue: 58(1), P. 81 - 97

Published: Jan. 2, 2023

The tricarboxylic acid (TCA) cycle is a primordial metabolic pathway that conserved from bacteria to humans. Although this network often viewed primarily as an energy producing engine fueling ATP synthesis via oxidative phosphorylation, mounting evidence reveals hub orchestrates wide variety of pivotal biological processes. It plays important part in combatting cellular stress by modulating NADH/NADPH homeostasis, scavenging ROS (reactive oxygen species), substrate-level signaling and supplying metabolites quell range disruptions. This review elaborates on how the reprogramming prompted such abiotic metal toxicity, tension, nutrient challenge antibiotic insult critical for countering these conditions mostly microbial systems. cross-talk between stressors participants TCA results changes metabolite nucleotide concentrations aimed at presented. fine-tuning mediated disparate enzymes associated with discussed. modulation enzymatic activities generating moieties dedicated respond perturbation explained. ancient has be recognized its ability execute plethora physiological functions beyond well-established traditional roles.

Language: Английский

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Role of amino acid metabolism in mitochondrial homeostasis

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 27, 2023

Mitochondria are central hubs for energy production, metabolism and cellular signal transduction in eukaryotic cells. Maintenance of mitochondrial homeostasis is important function survival. In particular, metabolic state constant communication with homeostasis. One the most processes that provide cell amino acid metabolism. Almost all 20 acids serve as building blocks proteins produced or degraded mitochondria. The synthesis aspartate arginine depends on activity respiratory chain, which essential proliferation. degradation branched-chain mainly occurs matrix, contributing to metabolism, biogenesis, well protein quality control both mitochondria cytosol. Dietary supplementation restriction worms, flies mice modulates lifespan health, has been associated changes antioxidant response, tricarboxylic cycle chain. Consequently, impaired primary diseases dysfunction such cancer. Here, we present recent observations crosstalk between homeostasis, summarise underlying molecular mechanisms date, discuss their role functions organismal physiology.

Language: Английский

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Metabolic regulation of the hallmarks of stem cell biology

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(2), P. 161 - 180

Published: Feb. 1, 2024

Language: Английский

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The Metabolic Syndrome, a Human Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2251 - 2251

Published: Feb. 13, 2024

This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy associated diseases/disorders, or just related rather independent pathologies. The human nature MS (its exceptionality in Nature and its close interdependence with action evolution) is presented discussed. text also describes components, special emphasis description their interrelations (including syndromic development recruitment), as well consequences upon energy handling partition. main theories MS’s origin are relation to hepatic steatosis, type 2 diabetes, obesity, encompass most components described so far. differential effects sex biological considered under light social needs evolution, which directly epidemiology, severity, relations senescence. triggering maintenance factors discussed, especial inflammation, complex process affecting different levels organization critical element for development. Inflammation operation connective tissue adipose organ) widely studied acknowledged influence diet. role diet composition, including transcendence anaplerotic Krebs cycle from dietary amino acid supply (and timing), developed context testosterone β-estradiol control insulin-glycaemia core system carbohydrate-triacylglycerol handling. high probability acting unique (essentially monophyletic) presented, together additional perspectives/considerations treatment this ‘very’ disease.

Language: Английский

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Physiologic disruption and metabolic reprogramming in infection and sepsis

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(5), P. 927 - 946

Published: March 20, 2024

Language: Английский

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Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 647 - 647

Published: Feb. 2, 2024

Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced death, known as cuproptosis, its disease implications, including cancer therapy. Copper ionophores, such elesclomol disulfiram, increase intracellular copper levels. elevation triggers oxidative stress subsequent offering implications in Additionally, ionophores disrupt mitochondrial respiration protein lipoylation, further contributing toxicity death. Potential targets biomarkers are identified, can be targeted those proteins trigger cuproptosis. The role different cancers is discussed understand therapies using nanomaterials, chelators. Furthermore, explored through diseases Wilson Menkes physiological copper. Exploring cuproptosis presents opportunity improve treatments copper-related disorders cancers, with bring significant advancements modern medicine.

Language: Английский

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Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 6, 2025

Abstract Hypoxia-inducible factors (HIFs) are essential transcription that orchestrate cellular responses to oxygen deprivation. HIF-1α, as an unstable subunit of HIF-1, is usually hydroxylated by prolyl hydroxylase domain enzymes under normoxic conditions, leading ubiquitination and proteasomal degradation, thereby keeping low levels. Instead hypoxia, sometimes even in normoxia, HIF-1α translocates into the nucleus, dimerizes with HIF-1β generate then activates genes involved adaptive such angiogenesis, metabolic reprogramming, survival, which presents new challenges insights its role processes. Thus, review delves mechanisms HIF-1 maintains stability normoxia including but not limited giving transcriptional, translational, well posttranslational regulation underscore pivotal adaptation malignancy. Moreover, extensively cancer cardiovascular diseases potentially serves a bridge between them. An overview HIF-1-related drugs approved or clinical trials summarized, highlighting their potential capacity for targeting toxicity related treatment. The provides comprehensive insight HIF-1’s regulatory mechanism paves way future research therapeutic development.

Language: Английский

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Rhodoquinone carries electrons in the mammalian electron transport chain

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Highlights•RQ is present in mitochondria isolated from certain mouse and human tissues•RQ carries electrons to fumarate as the electron acceptor, independently of O2 levels•The ETC can be reprogrammed RQ/fumarate pathway using genetic pharmacologic tools•Reprogramming mitigates hypoxia-induced damage vitro vivoSummaryUbiquinone (UQ), only known carrier mammalian transport chain (ETC), preferentially delivers terminal acceptor oxygen (O2). In hypoxia, ubiquinol (UQH2) diverts these onto instead. Here, we identify rhodoquinone (RQ), an detected purified tissues that through reversal succinate dehydrogenase, independent environmental levels. The strictly vivo undetectable cultured cells. Using tools reprogram UQ/O2 pathway, establish distinct ETCs support unique programs mitochondrial function RQ confers protection upon hypoxia exposure vivo. Thus, discovering presence mammals, unveil a tractable therapeutic strategy exploits flexibility ameliorate hypoxia-related conditions.Graphical abstract

Language: Английский

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Mitochondrial complex I inhibition triggers NAD+-independent glucose oxidation via successive NADPH formation, “futile” fatty acid cycling, and FADH2 oxidation

GeroScience, Journal Year: 2024, Volume and Issue: 46(4), P. 3635 - 3658

Published: Jan. 25, 2024

Abstract Inhibition of mitochondrial complex I (NADH dehydrogenase) is the primary mechanism antidiabetic drug metformin and various unrelated natural toxins. Complex inhibition can also be induced by PPAR agonists, it elicited methionine restriction, a nutritional intervention causing resistance to diabetes obesity. Still, comprehensible explanation why exerts properties engenders metabolic inefficiency missing. To evaluate this issue, we have systematically reanalyzed published transcriptomic datasets from MPP-treated neurons, metformin-treated hepatocytes, methionine-restricted rats. We found that pathways leading NADPH formation were widely induced, together with anabolic fatty acid biosynthesis, latter appearing highly paradoxical in state impairment. However, concomitant induction catabolic oxidation indicated created “futile” cycle synthesis degradation, which was anatomically distributed between adipose tissue liver vivo. Cofactor balance analysis unveiled such cycling would indeed energetically futile (-3 ATP per acetyl-CoA), though not redox-futile, as convert into respirable FADH 2 without any net production NADH. conclude NADH dehydrogenase leads shift glycolysis citric (both generating NADH) towards pentose phosphate pathway, whose product translated 1:1 cycling. The diabetes-resistant phenotype following hepatic intestinal attributed FGF21- GDF15-dependent fat hunger signaling, remodels glucose-metabolizing organ.

Language: Английский

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