Identification and validation of mitochondrial endoplasmic reticulum membrane-related genes in atherosclerosis

Mammalian Genome, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Language: Английский

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Lactate-Induced Mitochondrial Calcium Uptake 3 Aggravates Myocardial Ischemia-Reperfusion Injury by Promoting Neutrophil Extracellular Trap Formation

Research, Journal Year: 2025, Volume and Issue: 8

Published: Jan. 1, 2025

Background: Ischemic heart disease is a leading cause of mortality and disability worldwide among cardiovascular conditions. Myocardial ischemia–reperfusion injury (MIRI) occurs following percutaneous coronary intervention, during which neutrophils generate neutrophil extracellular traps (NETs) in response to injury. This study aims elucidate the mechanisms underlying NET activation its impact on MIRI. Methods: Sham MIRI rat models were established. Various techniques, including enzyme-linked immunosorbent assay, hematoxylin eosin staining, Masson transmission electron microscopy, used assess endothelial cell myocardial tissue inflammation. Immunofluorescence was employed evaluate tissues, peripheral blood neutrophils, protein colocalization. MitoTracker ER-Tracker staining conducted formation mitochondria-associated membranes (MAMs). Extracted NETs applied conduct microvascular tube assay flow cytometry. RNA-sequencing immunoprecipitation–mass spectrometry determine key regulators. Flow cytometry Western blot Ca 2+ mitophagy levels neutrophils. Deoxyribonuclease I, inhibitor, injected into rats vivo effects modulation severity. Results: often accompanied by cardiac (CMEC) Lactate mediated H3K18 lactylation at MICU3 promoter enhancing transcription elevated levels. Besides, lactate also promoted interaction between AASR1, stabilizing through lactylation. Up-regulated interacted with VDAC1, facilitating MAM formation, excessive uptake, mitochondrial dysfunction, activation, activation. Elevated level exacerbated CMEC further aggravating Conclusion: Lactate-driven transcriptional stabilization facilitates contributing development.

Language: Английский

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Identification and Validation of Key Genes Involved in the Coupling of Mitochondria-Associated Endoplasmic Reticulum Membrane in Hemorrhoidal Disease

International Journal of General Medicine, Journal Year: 2025, Volume and Issue: Volume 18, P. 2781 - 2798

Published: May 1, 2025

Hemorrhoidal disease (HD) is the most prevalent rectal disorder, with various cellular processes influenced by mitochondria-associated endoplasmic reticulum membrane (MAM). Potential therapeutic mechanisms for HD may be associated MAM. This study aims to identify key genes linked MAM in and provide novel targets. Transcriptome data MAM-related (MAM-RGs) were obtained from Gene Expression Omnibus (GEO) database relevant literature. Differential expression analysis single-sample Set Enrichment Analysis (ssGSEA) scores initially employed candidate genes. Key further refined using Least Absolute Shrinkage Selection Operator (LASSO) Protein-Protein Interaction (PPI) networks. A nomogram based on these was developed assessed. Additionally, CIBERSORT algorithms utilized evaluate immune cell infiltration abundance, differences, correlations samples. Finally, of validated via reverse transcription-quantitative PCR (RT-qPCR). identified 956 differentially expressed (DEGs), ssGSEA 143 MAM-RGs. total 50 selected through their intersection. Machine learning two genes, MUC16 DEFA5. strong predictive capability constructed. Immune revealed types differential cells-activated dendritic cells plasma cells-where activated more highly case group, showed a positive correlation significantly overexpressed patients HD, while DEFA5 exhibited down-regulation compared controls. identifies as presents high accuracy. These findings insights into potential treatment targets HD.

Language: Английский

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Endoplasmic reticulum-mitochondria crosstalk: new mechanisms in the development of atherosclerosis

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: June 5, 2025

Atherosclerosis (AS) is a global public health concern and involves complex pathogenesis characterized by lipid abnormalities, oxidative stress, inflammatory responses at the cellular molecular levels. The crosstalk between endoplasmic reticulum (ER) mitochondria, mediated mitochondria-associated membranes (MAMs), plays critical role in of atherosclerosis. As two key organelles, ER mitochondria interact physically functionally through MAMs, which serve as bridges their close contact interdependence. MAMs maintain homeostasis, promote calcium ion transport, stress response, apoptosis, autophagy. Recent studies have highlighted significance ER-mitochondria progression AS, indicated mitochondrial structural functional integrity, redox homeostasis. This review comprehensively explores novel mechanisms AS emphasizes potential therapeutic targets, aiming to provide new perspectives strategies for treatment cardiovascular diseases.

Language: Английский

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Mitochondrial Dysfunction in Cardiac Disease: The Fort Fell

Published: Oct. 12, 2024

Myocardial cells and extracellular matrix fulfil their goal thanks to the energetic availability. Indeed, mechanical electrical properties of heart are strongly depended on production-consumption equilibrium. The produced energy is used under several forms including kinetic, dynamic, thermal etc. Notably, as time goes by; aging well in case failure, although total remains almost constant contribution each form altered. Thermal increased, whereas dynamic kinetic decreased hence unable satisfy adequately cardiac work. Consequently, toxic products, unfolded /misfolded proteins, free radicals accumulated within myocardium. cell contraction – relaxation coupling, ion exchange, growth function failed, control apoptosis necrosis lacking micro macro-architecture change final result. Energy production consumption depends metabolic resources functional status silhouette cardiomyocytes non-cardiomyocytes - behavior. Mitochondria, intra-cellular organelles producing more than 95% ATP fulfill all above prerequisites being thus very important such we have better understand anatomy, homeostatic properties.

Language: Английский

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Mitochondrial Dysfunction in Cardiac Disease: The Fort Fell

Biomolecules, Journal Year: 2024, Volume and Issue: 14(12), P. 1534 - 1534

Published: Nov. 29, 2024

Myocardial cells and the extracellular matrix achieve their functions through availability of energy. In fact, mechanical electrical properties heart are heavily dependent on balance between energy production consumption. The produced is utilized in various forms, including kinetic, dynamic, thermal Although total remains nearly constant, contribution each form changes over time. Thermal increases, while dynamic kinetic decrease, ultimately becoming insufficient to adequately support cardiac function. As a result, toxic byproducts, unfolded or misfolded proteins, free radicals, other harmful substances accumulate within myocardium. This leads failure crucial processes such as myocardial contraction–relaxation coupling, ion exchange, cell growth, regulation apoptosis necrosis. Consequently, both micro- macro-architecture altered. Energy consumption depend heart’s metabolic resources functional state structure, cardiomyocytes, non-cardiomyocyte cells, energetic behavior. Mitochondria, which intracellular organelles that produce more than 95% ATP, play critical role fulfilling all these requirements. Therefore, it essential gain deeper understanding anatomy, function, homeostatic properties.

Language: Английский

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Mitofusin 2 inhibits high glucose-induced apoptosis of human lens epithelial cells via modulating mitochondrial function and autophagy

Folia Histochemica et Cytobiologica, Journal Year: 2024, Volume and Issue: 62(2), P. 76 - 86

Published: July 30, 2024

Introduction. Diabetic cataract (DC) is a common ocular complication of diabetes. Mitofusin 2 (MFN2), mitochondrial fusion protein, involved in the pathogenesis and diabetic complications. However, its role molecular mechanisms DC remain unclear. Materials methods. models rats were induced by intraperitoneal injection streptozocin (STZ) for 12 weeks. We measured body weight rats, blood glucose concentrations, sorbitol dehydrogenase (SDH) activity advanced glycation end products (AGE) content lenses rats. MFN2 mRNA protein expression levels detected RT-qPCR western blot assays. In vitro , human lens epithelial (HLE) B3 cells treated 48 h with 25 mM (high glucose, HG) to induce cell damage. To determine HG-induced damage, HLE-B3 transfected lentivirus loaded overexpression plasmid or short hairpin RNA (shRNA) overexpress knock down expression, followed HG exposure. Cell viability was assessed CCK-8 assay. Flow cytometry used detect apoptosis reactive oxygen species (ROS) level. JC-1 staining showed changes membrane potential (Δψm). The mediators related apoptosis, autophagy determined. Results. STZ-administrated reduced weight, increased levels, elevated SDH AGE content, suggesting successful establishment rat model. Interestingly, significantly downregulated cells. Further analysis that under conditions, enhanced inhibited accompanied decreased Bax, cleaved caspase-9 Bcl-2 also suppressed damage elicited as manifested ROS production, recovered Δψm cytochrome c (Cyto c) Moreover, LC3BⅡ/LC3BⅠ ratio Beclin-1 but p62 level, blocked phosphorylation mTOR HG-treated contrast, silencing exerted opposite effects. Conclusions. Our findings indicate may be essential preventing during development cataract.

Language: Английский

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Inter- and intracellular mitochondrial communication: signaling hubs in aging and age-related diseases

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Dec. 18, 2024

Abstract Mitochondria are versatile and complex organelles that can continuously communicate interact with the cellular milieu. Deregulated communication between mitochondria host cells/organelles has significant consequences is an underlying factor of many pathophysiological conditions, including process aging. During aging, lose function, mitocellular pathways break down; mitochondrial dysfunction interacts dyscommunication, forming a vicious circle. Therefore, strategies to protect function promote effective increase healthy lifespan longevity, which might be new treatment paradigm for age-related disorders. In this review, we comprehensively discuss signal transduction mechanisms inter- intracellular communication, as well interactions hallmarks This review emphasizes indispensable position in aging organisms, crucial signaling hubs. addition, also specifically focus on status mitochondria-targeted interventions provide potential therapeutic targets diseases. Graphical

Language: Английский

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