Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(8), С. 3923 - 3923

Опубликована: Апрель 10, 2021

Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified PCOS patients likely play an important role aetiology pathogenesis; however, their causative development requires further investigation. As low-grade chronic inflammation disease, permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding mutations malfunctions pathogenesis. Furthermore, discuss papers dedicated to identification novel biomarkers for early diagnosis. Finally, traditional new mitochondria-targeted treatments are discussed. This review intends emphasise key oxidative stress exact molecular mechanism mostly unknown

Язык: Английский

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Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature

Current Environmental Health Reports, Год журнала: 2022, Номер 9(4), С. 631 - 649

Опубликована: Июль 28, 2022

Abstract Purpose of Review Mitochondria play various roles that are important for cell function and survival; therefore, significant mitochondrial dysfunction may have chronic consequences extend beyond the cell. already susceptible to damage, which be exacerbated by environmental exposures. Therefore, aim this review is summarize recent literature (2012–2022) looking at effects six ubiquitous classes compounds on in human populations. Recent Findings The suggests there a number biomarkers commonly used identify dysfunction, each with certain advantages limitations. Classes toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, nanomaterials can damage mitochondria varied ways, changes mtDNA copy measures oxidative most measured Other include membrane potential, calcium levels, ATP levels. Summary This identifies characterize but emerging biomarkers, cell-free blood cardiolipin provide greater insight into impacts exposures function. using novel approaches addition well-characterized ones create standardized protocols. We identified dearth studies populations exposed chemicals, nanoparticles gap knowledge needs attention.

Язык: Английский

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Exposure to nanoplastics induces mitochondrial impairment and cytomembrane destruction in Leydig cells

Ecotoxicology and Environmental Safety, Год журнала: 2023, Номер 255, С. 114796 - 114796

Опубликована: Март 20, 2023

Plastic particle pollution poses an emerging threat to ecological and human health. Laboratory animal studies have illustrated that nano-sized plastics can accumulate in the testis cause testosterone deficiency spermatogenic impairment. In this study, TM3 mouse Leydig cells were vitro exposed polystyrene nanoparticles (PS-NPs, size 20 nm) at dosages of 50, 100 150 μg/mL investigate their cytotoxicity. Our results demonstrated PS-NPs be internalized into led a concentration-dependent decline cell viability. Furthermore, stimulation amplified ROS generation initiated cellular oxidative stress apoptosis. Moreover, treatment affected mitochondrial DNA copy number collapsed membrane potential, accompanied by disrupted energy metabolism. The also displayed down-regulated expression steroidogenesis-related genes StAR, P450scc 17β-HSD, along with decrease secretion. addition, destructed plasma integrity, as presented increase lactate dehydrogenase release depolarization potential. summary, these data indicated exposure produced cytotoxic effect on inducing injury, impairment, apoptosis, cytomembrane destruction. provide new insights male reproductive toxicity caused NPs.

Язык: Английский

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Mitochondria in Alzheimer’s Disease Pathogenesis

Life, Год журнала: 2024, Номер 14(2), С. 196 - 196

Опубликована: Янв. 30, 2024

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years above. It causes dementia with memory loss deterioration in thinking language skills. AD characterized by specific pathology resulting from the accumulation brain of extracellular plaques amyloid-β intracellular tangles phosphorylated tau. The importance mitochondrial dysfunction pathogenesis, while previously underrecognized, now more appreciated. Mitochondria are an essential organelle involved cellular bioenergetics signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, trafficking, fission, fusion dysregulated brain. Excess fission fragmentation yield mitochondria low energy production. Reduced glucose metabolism also observed hypometabolic state, particularly temporo-parietal regions. This review addresses multiple ways which abnormal structure function contribute to AD. Disruption electron transport chain ATP production neurotoxic because cells have disproportionately high demands. In addition, oxidative stress, extremely damaging nerve cells, rises dramatically dyshomeostasis. Restoring health may be viable approach treatment.

Язык: Английский

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Mitochondrial DNA Copy Number as a Potential Biomarker for the Severity of Motor Symptoms and Prognosis in Parkinson's Disease

Movement Disorders, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Mitochondrial function influences Parkinson's disease (PD) through the accumulation of pathogenic alpha-synuclein, oxidative stress, impaired autophagy, and neuroinflammation. The mitochondrial DNA copy number (mtDNA-CN), representing copies within a cell, serves as an easily assessable proxy for function.

Язык: Английский

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Engineered mitochondria in diseases: mechanisms, strategies, and applications

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

Опубликована: Март 3, 2025

Abstract Mitochondrial diseases represent one of the most prevalent and debilitating categories hereditary disorders, characterized by significant genetic, biological, clinical heterogeneity, which has driven development field engineered mitochondria. With growing recognition pathogenic role damaged mitochondria in aging, oxidative inflammatory diseases, cancer, application expanded to those non-hereditary contexts (sometimes referred as mitochondria-related diseases). Due their unique non-eukaryotic origins endosymbiotic relationship, are considered highly suitable for gene editing intercellular transplantation, remarkable progress been achieved two promising therapeutic strategies—mitochondrial artificial mitochondrial transfer (collectively this review) over past decades. Here, we provide a comprehensive review mechanisms recent advancements applications, alongside concise summary potential implications supporting evidence from preclinical studies. Additionally, an emerging potentially feasible approach involves ex vivo editing, followed selection holds overcome limitations such reduced operability introduction allogeneic thereby broadening applicability

Язык: Английский

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Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease

Genome Research, Год журнала: 2021, Номер 31(3), С. 349 - 358

Опубликована: Янв. 13, 2021

Mitochondrial DNA copy number (mtDNA-CN) is a proxy for mitochondrial function and associated with aging-related diseases. However, it unclear how mtDNA-CN measured in blood can reflect diseases that primarily manifest other tissues. Using the Genotype-Tissue Expression Project, we interrogated relationships between whole gene expression from 47 additional tissues 419 individuals. was significantly of 700 genes blood, including nuclear required mtDNA replication. Significant enrichment observed splicing ubiquitin-mediated proteolysis pathways, as well target transcription factor NRF1. In nonblood tissues, there were more than expected 30 suggesting global those correlated blood-derived mtDNA-CN. Neurodegenerative disease pathways multiple an independent data set, UK Biobank, higher lower rates both prevalent (OR = 0.89, CI 0.83; 0.96) incident neurodegenerative (HR 0.95, 95% 0.91;0.98). The observation suggests metabolic health across Identification key splicing, RNA binding, catalysis reinforces importance mitochondria maintaining cellular homeostasis. Finally, validation role CN large cohort study solidifies link mtDNA-CN, altered disease.

Язык: Английский

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Integrating DNA Methylation Measures of Biological Aging into Social Determinants of Health Research

Current Environmental Health Reports, Год журнала: 2022, Номер 9(2), С. 196 - 210

Опубликована: Фев. 18, 2022

Язык: Английский

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Major depression and the biological hallmarks of aging

Ageing Research Reviews, Год журнала: 2022, Номер 83, С. 101805 - 101805

Опубликована: Ноя. 21, 2022

Major depressive disorder (MDD) is characterized by psychological and physiological manifestations contributing to the disease severity outcome. In recent years, several lines of evidence have suggested that individuals with MDD an elevated risk age-related adverse outcomes across lifespan. This review provided a significant overlap between biological abnormalities in changes commonly observed during aging process (i.e., hallmarks aging). Based on such evidence, we formulate mechanistic model showing how can be common denominator mediate health MDD. Finally, proposed roadmap for novel studies investigate intersection biology MDD, including use geroscience-guided interventions, as senolytics, delay or improve major depression targeting aging.

Язык: Английский

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DNA Damage-Induced Inflammatory Microenvironment and Adult Stem Cell Response

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Окт. 8, 2021

Adult stem cells ensure tissue homeostasis and regeneration after injury. Due to their longevity functional requirements, throughout life are subject a significant amount of DNA damage. Genotoxic stress has recently been shown trigger cascade cell- non-cell autonomous inflammatory signaling pathways, leading the release pro-inflammatory factors an increase in infiltrating immune cells. In this review, we discuss recent evidence how damage by affecting microenvironment present adult tissues neoplasms can affect maintenance long-term function. We first focus on importance self-DNA sensing immunity activation, inflammation secretion mediated activation cGAS-STING pathway, ZBP1 pathogen sensor, AIM2 NLRP3 inflammasomes. Alongside cytosolic DNA, emerging roles double-stranded RNA mitochondrial discussed. The response also initiate mechanisms limit division damaged stem/progenitor inducing permanent state cell cycle arrest, known as senescence. Persistent triggers senescent secrete senescence-associated secretory phenotype (SASP) factors, which act strong modulators. Altogether these damage-mediated immunomodulatory responses have tissue-specific degenerative conditions. Conversely, specific cytokines positively impact plasticity addition enhancing activity cancer thereby driving tumor progression. Further mechanistic understanding damage-induced might shed light age-related diseases cancer, potentially inform novel treatment strategies.

Язык: Английский

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