Mitochondrial Heteroplasmy Shifting as a Potential Biomarker of Cancer Progression DOI Open Access
Carlos Jhovani Pérez-Amado, Amellalli Bazan-Cordoba, Alfredo Hidalgo‐Miranda

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(14), P. 7369 - 7369

Published: July 9, 2021

Cancer is a serious health problem with high mortality rate worldwide. Given the relevance of mitochondria in numerous physiological and pathological mechanisms, such as adenosine triphosphate (ATP) synthesis, apoptosis, metabolism, cancer progression drug resistance, mitochondrial genome (mtDNA) analysis has become great interest study human diseases, including cancer. To date, number variants mutations have been identified different types tumors, which coexist normal alleles, phenomenon named heteroplasmy. This mechanism considered an intermediate state between fixation or elimination acquired mutations. It suggested that mutations, confer adaptive advantages to tumor growth invasion, are enriched malignant cells. Notably, many recent studies reported heteroplasmy-shifting potential shaper treatment response, we suggest each type also unique profile. So far, plethora data evidencing correlations among heteroplasmy cancer-related phenotypes available, but still, not authentic demonstrations, whether variation mtDNA copy (mtCNV) cause consequence remained unknown. Further needed support these findings decipher their clinical implications impact field discovery aimed at treating

Language: Английский

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome DOI Open Access
Siarhei A. Dabravolski, Nikita G. Nikiforov, Ali H. Eid

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(8), P. 3923 - 3923

Published: April 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

Language: Английский

Citations

117
Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature DOI Creative Commons
Aalekhya Reddam, Sarah M. McLarnan, Allison Kupsco

et al.

Current Environmental Health Reports, Journal Year: 2022, Volume and Issue: 9(4), P. 631 - 649

Published: July 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.

Language: Английский

Citations

74
Exposure to nanoplastics induces mitochondrial impairment and cytomembrane destruction in Leydig cells DOI Creative Commons

Zhangbei Sun,

Yiqian Wen,

Fan Zhang

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 255, P. 114796 - 114796

Published: March 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.

Language: Английский

Citations

56
Mitochondria in Alzheimer’s Disease Pathogenesis DOI Creative Commons
Allison B. Reiss,

Shelly Gulkarov,

Benna Jacob

et al.

Life, Journal Year: 2024, Volume and Issue: 14(2), P. 196 - 196

Published: Jan. 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.

Language: Английский

Citations

26
Mitochondrial DNA Copy Number as a Potential Biomarker for the Severity of Motor Symptoms and Prognosis in Parkinson's Disease DOI Open Access
Sungyang Jo, Ji‐Hye Oh, Eun‐Jae Lee

et al.

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

2
Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease DOI Creative Commons
Stephanie Yang, Christina A. Castellani, Ryan J. Longchamps

et al.

Genome Research, Journal Year: 2021, Volume and Issue: 31(3), P. 349 - 358

Published: Jan. 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.

Language: Английский

Citations

80
Integrating DNA Methylation Measures of Biological Aging into Social Determinants of Health Research DOI
Laurel Raffington, Daniel W. Belsky

Current Environmental Health Reports, Journal Year: 2022, Volume and Issue: 9(2), P. 196 - 210

Published: Feb. 18, 2022

Language: Английский

Citations

65
Major depression and the biological hallmarks of aging DOI Creative Commons

Erica C. Lorenzo,

George A. Kuchel, Chia‐Ling Kuo

et al.

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 83, P. 101805 - 101805

Published: Nov. 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.

Language: Английский

Citations

60
Prospective Associations of Early Pregnancy Metal Mixtures with Mitochondria DNA Copy Number and Telomere Length in Maternal and Cord Blood DOI Creative Commons
Anna R. Smith, Pi‐I D. Lin, Sheryl L. Rifas‐Shiman

et al.

Environmental Health Perspectives, Journal Year: 2021, Volume and Issue: 129(11)

Published: Nov. 1, 2021

Metal exposure during pregnancy influences maternal and child health. Oxidative stress inflammation may mediate adverse effects of heavy metals, whereas essential metals act as antioxidants. Mitochondrial DNA is a prime target for metal-induced oxidative damage. Telomere dysfunction attributed to imbalances between reactive oxidant species antioxidants.We evaluated individual joint associations prenatal with mitochondrial copy number (mtDNAcn) telomere length (TL) in cord blood biomarkers stress.We measured six nonessential (arsenic, barium, cadmium, cesium, lead, mercury) four (magnesium, manganese, selenium, zinc) first-trimester red cells Project Viva, U.S. prebirth cohort. We relative mtDNAcn (n=898) TL (n=893) second-trimester (n=419) (n=408) blood. used multivariable linear regression quantile g-computation estimate the biomarkers. generalized additive models Bayesian kernel machine examine nonlinearity interactions.A 2-fold increase magnesium was associated lower [β=-0.07, 95% confidence interval (CI): -0.10, -0.01] (β=-0.08, CI: -0.20, -0.01) mtDNAcn. Lead higher (β=0.04, 0.01, 0.06). Selenium longer (β=0.30, 0.01 0.50). An association observed metal mixture 0.07). There nonlinear relationship magnesium; mercury; barium.Maternal such magnesium, selenium second trimester Future work will evaluate whether these are https://doi.org/10.1289/EHP9294.

Language: Английский

Citations

57
PGC-1a mediated mitochondrial biogenesis promotes recovery and survival of neuronal cells from cellular degeneration DOI Creative Commons
Wenting You, Kèvin Knoops, Tos T. J. M. Berendschot

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 17, 2024

Abstract Neurodegenerative disorders are characterized by the progressive loss of structure and function neurons, often including death neuron. Previously, we reported that, removing cell stimulus, dying/injured neurons could survive recover from process regulated death, even if cells already displayed various signs cellular damage. Now investigated role mitochondrial dynamics (fission/fusion, biogenesis, mitophagy) in both degeneration recovery neuronal cells. In PC12 cells, exposure to ethanol (EtOH) induced massive neurite along with widespread fragmentation, membrane potential loss, reduced ATP production, decreased total volume. By EtOH timely all these parameters recovered normal levels. Meanwhile, regrew neurites survived. Study showed that autophagy was activated only during phase (EtOH treatment) but not removed), it dependent on Parkin/PINK1 mediated mitophagy pathway. Protein expression key regulators fission, phospho-Drp1 Ser616 S-OPA1, increased treatment levels after EtOH. addition, critical PGC-1α biogenesis revealed: inhibition using SR-18292 removal significantly impeded damage, regeneration neurites, survival a concentration-dependent manner. Taken together, our study reversibility morphological functional damage stressed revealed played recovery. This molecular mechanism be target for neuroprotection neurorescue neurodegenerative diseases.

Language: Английский

Citations

12