Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics

Redox Biology, Год журнала: 2024, Номер 70, С. 103049 - 103049

Опубликована: Янв. 20, 2024

Once thought of in terms bioenergetics, mitochondria are now widely accepted as both the orchestrator cellular health and gatekeeper cell death. The pulmonary disease field has performed extensive efforts to explore role regulating inflammation, metabolism, apoptosis, oxidative stress. However, a critical component these processes needs be more studied: mitochondrial network dynamics. Mitochondria morphologically change response their environment regulate through fusion, fission, mitophagy. This allows adapt function respond requirements, maintaining homeostasis. For that reason, dynamics can considered bridge brings multiple together, revealing potential pathway for therapeutic intervention. In this review, we discuss modulators how they affected diseases, including chronic obstructive (COPD), idiopathic fibrosis (IPF), acute lung injury (ALI), arterial hypertension (PAH). A dysregulated plays crucial pathobiology, aberrant fission/fusion/mitophagy pathways druggable warrant further exploration. Thus, also candidates therapeutics

Язык: Английский

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Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Язык: Английский

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Targeting organ-specific mitochondrial dysfunction to improve biological aging

Pharmacology & Therapeutics, Год журнала: 2024, Номер 262, С. 108710 - 108710

Опубликована: Авг. 22, 2024

In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites key regulators programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, mitochondrial dysfunction pivotal factor progressive age-related decline cellular homeostasis organ function. The current review examines recent advances understanding interplay between organ-specific aging. Thereby, we dissect molecular mechanisms underlying impairment associated with deterioration exploring DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated patterns, biogenesis, turnover, dynamics. We also highlight emerging therapeutic preclinical clinical tests that supposed rejuvenate such as antioxidants, biogenesis stimulators, modulators turnover Furthermore, discuss potential benefits challenges use interventions, emphasizing need for approaches given unique characteristics different tissues. conclusion, this highlights addressing mitigate aging, focusing on skin, liver, lung, brain, skeletal muscle, well reproductive, immune, cardiovascular systems. Based comprehensive multifaceted roles mitochondria, innovative may be developed optimized biological promote healthy across diverse

Язык: Английский

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Mitochondrial fission produces a Warburg effect via the oxidative inhibition of prolyl hydroxylase domain-2

Redox Biology, Год журнала: 2025, Номер 81, С. 103529 - 103529

Опубликована: Фев. 4, 2025

Excessive mitochondrial fission and a shift to Warburg phenotype are hallmarks of pulmonary hypertension (PH), although the mechanistic link between these processes remains unclear. We show that in arterial endothelial cells (PAEC), Drp1 overexpression induces increases glycolytic ATP production glycolysis. This is due reactive oxygen species (mito-ROS)-mediated activation hypoxia-inducible factor-1α (HIF-1α) signaling, this linked hydrogen peroxide (H2O2)-mediated inhibition prolyl hydroxylase domain-2 (PHD2) its cysteine 326 oxidation dimerization. Furthermore, findings validated PAEC isolated from lamb model PH, which (Shunt PAEC), exhibit both H2O2 PHD2 dimer levels. The catalase reversed dimerization, decreased HIF-1α levels, attenuated glycolysis Shunt PAEC. Our data suggest reducing dimerization could be potential therapeutic target for PH.

Язык: Английский

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Analyzing the molecular mechanism of xuefuzhuyu decoction in the treatment of pulmonary hypertension with network pharmacology and bioinformatics and verifying molecular docking

Computers in Biology and Medicine, Год журнала: 2023, Номер 169, С. 107863 - 107863

Опубликована: Дек. 30, 2023

Язык: Английский

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Promising dawn in the management of pulmonary hypertension: The mystery veil of gut microbiota

iMeta, Год журнала: 2024, Номер 3(2)

Опубликована: Янв. 1, 2024

Abstract The gut microbiota is a complex community of microorganisms inhabiting the intestinal tract, which plays vital role in human health. It intricately involved metabolism, and it also affects diverse physiological processes. gut–lung axis bidirectional pathway between gastrointestinal tract lungs. Recent research has shown that microbiome crucial immune response regulation lungs development lung diseases. In this review, we present interrelated factors concerning associated metabolites pulmonary hypertension (PH), lethal disease characterized by elevated vascular pressure resistance. Our team explored gut‐microbiota‐derived cardiovascular diseases established correlation such as putrescine, succinate, trimethylamine N‐oxide (TMAO), N, N‐trimethyl‐5‐aminovaleric acid with Furthermore, found specific metabolites, TMAO betaine, have significant clinical value PH, suggesting their potential biomarkers management. detailing interplay microbiota, underscored therapeutic approaches modulating microbiota. Ultimately, endeavor to alleviate substantial socioeconomic burden disease. This review presents unique exploratory analysis link intending propel further investigations axis.

Язык: Английский

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Strategic disruption of cancer’s powerhouse: precise nanomedicine targeting of mitochondrial metabolism

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 8, 2024

Abstract Mitochondria occupy a central role in the biology of most eukaryotic cells, functioning as hub oxidative metabolism where sugars, fats, and amino acids are ultimately oxidized to release energy. This crucial function fuels variety cellular activities. Disruption mitochondrial is common feature many diseases, including cancer, neurodegenerative conditions cardiovascular diseases. Targeting tumor cell with multifunctional nanosystems emerges promising strategy for enhancing therapeutic efficacy against cancer. review comprehensively outlines pathways metabolism, emphasizing their critical roles energy production metabolic regulation. The associations between aberrant initiation progression cancer highlighted, illustrating how these disruptions contribute oncogenesis sustainability. More importantly, innovative strategies employing nanomedicines precisely target therapy fully explored. Furthermore, key challenges future directions this field identified discussed. Collectively, provides comprehensive understanding current state potential nanomedicine targeting offering insights developing more effective therapies.

Язык: Английский

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Antioxidant effects of Paeoniflorin and relevant molecular mechanisms as related to a variety of diseases: A review

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116772 - 116772

Опубликована: Май 28, 2024

Paeoniflorin (PF), which is the main component of Paeonia lactiflora Pall extract, one traditional Chinese medicines. The pharmacological effects associated with PF include antioxidant, immunomodulatory, anti-inflammatory, anticancer, antidepressant-like and neuroprotective effects. Our previous studies had revealed that protected melanocytes inhibited photodamage through suppression oxidative stress (OS). As OS plays a vital role in progression variety diseases, capacity for to suppress may exert important upon them. However, no review exists on these antioxidant as related various diseases. Therefore, this we summarized involved examining molecular mechanisms PF. Through its inhibit OS, has been shown beneficial several systems including nervous, cardiac/vascular, digestive, respiratory well specific diseases such diabetes, autoimmune, pregnancy related, ocular, kidney, dermatology, along distal flap necrosis, postoperative adhesions, hearing loss. Such findings provide new insights directions future research directed at development natural treatment clinical

Язык: Английский

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Critical Role of Mitochondrial Fatty Acid Metabolism in Normal Cell Function and Pathological Conditions

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6498 - 6498

Опубликована: Июнь 12, 2024

There is a “popular” belief that fat-free diet beneficial, supported by the scientific dogma indicating high levels of fatty acids promote many pathological metabolic, cardiovascular, and neurodegenerative conditions. This pressured scientists not to recognize essential role in cellular metabolism focus on detrimental effects acids. In this work, we critically review several decades studies recent publications supporting critical mitochondrial acid homeostasis Fatty are primary fuel source cell membrane building blocks from origin life. The membranes phospholipids were evolutionarily preserved earlier bacteria human subjects. past century, discovery was superseded epidemic growth metabolic conditions cardiovascular diseases. association due their “harmful” but rather result impaired abnormal lifestyle. Mitochondrial dysfunction linked drives multiple Despite flexibility, loss oxidation cannot be fully compensated for other sources substrates, such as carbohydrates amino acids, resulting pathogenic accumulation long-chain deficiency medium-chain popular belief, only energy-demanding organs heart, skeletal muscle, kidneys also metabolically “inactive” endothelial epithelial cells. Recent indicate specific tissues support cell- tissue-specific fashion. therefore, provides basis challenge these established dogmas articulate need paradigm shift “pathogenic” oxidation. important define causative develop novel therapeutic approaches targeting metabolism.

Язык: Английский

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Glucose metabolism impairment in major depressive disorder

Brain Research Bulletin, Год журнала: 2025, Номер 221, С. 111191 - 111191

Опубликована: Янв. 7, 2025

Major depressive disorder (MDD) is a common mental with chronic tendencies that seriously affect regular work, life, and study. However, its exact pathogenesis remains unclear. Patients MDD experience systemic localized impairments in glucose metabolism throughout the disease course, disrupting various processes such as uptake, glycoprotein transport, glycolysis, tricarboxylic acid cycle (TCA), oxidative phosphorylation (OXPHOS). These may result from mechanisms including insulin resistance, hyperglycemia-induced damage, stress, astrocyte abnormalities, mitochondrial dysfunction, leading to insufficient energy supply, altered synaptic plasticity, neuronal cell death, functional structural damage reward networks. mechanical changes contribute of severely interfere prognosis. Herein, we summarized impairment pathophysiological patients MDD. In addition, briefly discussed potential pharmacological interventions for alleviate MDD, glucagon-like peptide-1 receptor agonists, metformin, topical insulin, liraglutide, pioglitazone, encourage development new therapeutics.

Язык: Английский

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