Serum starvation induces cytosolic DNA trafficking via exosome and autophagy-lysosome pathway in microglia DOI Creative Commons
Liyan Zhou, Zilong Wu, Xiaoqing Yi

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 23, 2024

Abstract The imbalance of microglial homeostasis is highly associated with age-related neurological diseases, where cytosolic endogenous DNA also likely to be found. However, the intracellular trafficking remains unidentified. In this study, we demonstrated that nuclear (nDNA) and mitochondrial (mtDNA) undergo different under conditions induced by serum starvation. Upon detecting various components in cytoplasmic extracellular microglia, found nDNA primarily exists a free form undergoes degradation through autophagy-lysosome pathway. contrast, mtDNA predominantly membrane-wrapped trafficked both exosome pathways, which are key biomolecule trafficking. When pathway was inhibited, there an increase exosomes. More importantly, inhibition resulted enhanced These findings unveiled crosstalk between these two pathways thus provide new insights into intervening diseases.

Language: Английский

Serum starvation induces cytosolic DNA trafficking via exosome and autophagy-lysosome pathway in microglia DOI
Liyan Zhou, Zilong Wu, Xiaoqing Yi

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 119905 - 119905

Published: Jan. 1, 2025

Language: Английский

Citations

0
Upregulation of Autophagy During the Differentiation of Primary Human Term Cytotrophoblast Cells into Syncytial Cells: Ultrastructural Analysis DOI Open Access

Shohei Tozawa,

Hironori Takahashi, Syunya Noguchi

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1321 - 1321

Published: Feb. 4, 2025

The villous trophoblast cells are of fundamental importance because they fulfill a variety functions that vital for the growth fetus and maintenance pregnancy. A simple in vitro cell model grows on standard tissue culture plates has been utilized various functional studies cells. Despite potential value incorporating electron microscopy analysis reports primary human cells, is exclusively ancillary to previous publications. In context autophagy research using detailed ultrastructural flux imperative; however, it not conducted date. this study, we isolated term (i.e., cytotrophoblast CTB cells) most up-to-date isolation method isolating pure from placenta investigated dynamic process cultured by means transmission microscopy. initial 6 h resulted aggregation; majority did differentiate into syncytial contrast, after 72 h, exhibited promotion differentiation revealed upregulation visualized unique autophagic profiles during which perinuclear accumulation extremely large autophagosomes/autolysosomes. This study provides novel insights reproductive biology thereby demonstrating substantial as resources.

Language: Английский

Citations

0
Stroma-driven horizontal transfer of TCA proteins mediates metabolic plasticity and imatinib resistance in leukemia DOI Creative Commons
Katarzyna Piwocka, Piotr Chrościcki,

Nikodem Kasak

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract Leukemia cells residing in the bone marrow often exhibit resistance to tyrosine kinase inhibitors. Metabolic rearrangement of cancer has recently gained particular attention as a possible cause adaptation and insensitivity drug treatment. We demonstrated here that stromal directly transferred membrane vesicles together with proteins related tricarboxylic acid (TCA/Krebs) cycle leukemic cells. This transfer was dependent on direct cell-to-cell contact led increased metabolic plasticity. In addition, co-culture activities TCA cycle, oxidative phosphorylation capacity, therefore protected from loss homeostasis stress response imatinib. As result stroma, reductions OXPHOS, mitochondria-related parameters maximal respiration observed imatinib-treated cells, were substantially less present, spare respiratory capacity parameter even higher compared control Metabolome profiling revealed co-cultured treated imatinib levels TCA-related metabolites such isocitric acid, L-malic ketoglutaric cis-aconitic well lower level stress. The rho0 analysis horizontal GFP-positive mitochondria excluded their status important for stroma-driven protection. Altogether, our data provide insight into novel mechanism marrow-mediated protection associated plasticity driver been indicated leukemia stem however indicate presence may support all conclusion, we postulate elements involved can be targeted achieve therapeutic effect overcome caused by microenvironment.

Language: Английский

Citations

0
Oxidative Stress, Gut Microbiota, and Extracellular Vesicles: Interconnected Pathways and Therapeutic Potentials DOI Open Access
Bo Ma, Muttiah Barathan, Min Hwei Ng

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3148 - 3148

Published: March 28, 2025

Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development progression of chronic diseases. This review provides comprehensive analysis complex interplay between these two factors, focusing on how an imbalance reactive oxygen species (ROS) antioxidants leads to OS, disrupting cellular homeostasis contributing range conditions, including metabolic disorders, cardiovascular diseases, neurological cancer. The microbiota, diverse community microorganisms residing gastrointestinal tract, is essential for regulating immune responses, pathways, overall health. Dysbiosis, composition, closely associated with inflammation, dysfunction, various highlights influences influenced by complicating pathophysiology many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators crosstalk OS microbiota. EVs also play signaling host tissues, modulating processes. function holds promise targeted therapies aimed at restoring microbial balance mitigating OS. Personalized therapeutic approaches, probiotics, antioxidants, fecal transplantation-based strategies, can be used address OS-related diseases improve health outcomes. Nonetheless, further research needed study molecular mechanisms underlying interactions potential innovative interventions offer novel strategies managing enhancing

Language: Английский

Citations

0
In vitro study on the promotion of osteogenic differentiation by mitochondrial-derived vesicles through activation of inflammation and reprogramming of metabolic pathways DOI Creative Commons
Chun Pan,

Cheng Cheng,

Zhong Shu

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: April 17, 2025

The secretion of mitochondrial-derived vesicles (MDVs) has been found to increase during osteogenic differentiation, but their role in intercellular communication and promotion remains unclear. In this study, we extracted translocase outer mitochondrial membrane 20 (Tomm20) + MDVs from bone marrow stromal cells (BMSCs) at different culture days using differential centrifugation immunoprecipitation, then co-cultured them with BMSCs assess immune response metabolic levels. results showed that differentiation enhances MDVs' DNA (mtDNA) content. promoting ability, osteogenic-induced (MDV-OMs, especially MDV-OM14 MDV-OM21) significantly enhance mineralization OD values 1.37-fold 1.32-fold higher than those MDV-OM7 (p < 0.05) after 21 days, respectively. However, these containing mtDNA activate responses by upregulating cGas, Sting, Caspase-9, Il-6, Tnf-a mRNA levels, inducing cell apoptosis oxidative stress. addition, components also have regulatory functions. Metabolic level detection revealed MDV-OMs downregulate lactate, promote tricarboxylic acid cycle (TCA) enzyme expression, potential. Among MDVs, MDV-OM7, induced for 7 shows function without strong response, possibly related reprogramming. This study highlights the potential regeneration, cGAS-STING activation, enhancement, are expected be used treatment diseases such as tissue damage.

Language: Английский

Citations

0
CNS Mitochondria‐Derived Vesicle in Blood: Potential Biomarkers for Brain Mitochondria Dysfunction DOI Creative Commons
Qi Liu, Wentao Chen, Yahong Wu

et al.

Annals of Clinical and Translational Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

ABSTRACT Objective Mitochondrial dysfunction is a hallmark of neurodegenerative diseases like Alzheimer's (AD) and Parkinson's (PD). Our goal was to develop practical, noninvasive methods assess mitochondrial status through the detection mitochondria‐derived vesicles (MDVs). Methods We explored blood‐borne MDVs, recently identified class extracellular vesicles, as potential biomarkers for CNS status. Results The study MDVs from neurons, astrocytes, oligodendrocytes specifically in human plasma. A novel nanoflow cytometry developed evaluate level neuron‐, astrocyte‐, oligodendrocyte‐derived plasma AD PD patients. Importantly, analyses discovery validation cohorts revealed significantly lower brain cell‐specific patients compared healthy controls. Interpretation This suggests that blood could serve AD, PD, beyond, potentially aiding monitoring mitochondrial‐focused therapies neurological disorders.

Language: Английский

Citations

0
Mitochondria-Derived Vesicles, Sterile Inflammation, and Pyroptosis in Liver Cancer: Partners in Crime or Innocent Bystanders? DOI Open Access
Flora Guerra, Francesca Romana Ponziani,

Ferdinando Cardone

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4783 - 4783

Published: April 27, 2024

Alterations in cellular signaling, chronic inflammation, and tissue remodeling contribute to hepatocellular carcinoma (HCC) development. The release of damage-associated molecular patterns (DAMPs) upon injury the ensuing sterile inflammation have also been attributed a role HCC pathogenesis. Cargoes extracellular vesicles (EVs) and/or EVs themselves listed among circulating DAMPs but only partially investigated HCC. Mitochondria-derived (MDVs), subpopulation EVs, are another missing link comprehension mechanisms underlying onset progression biology. involved growth, dissemination, angiogenesis, immunosurveillance escape. contribution MDVs these processes is presently unclear. Pyroptosis triggers systemic through caspase-dependent apoptotic cell death implicated tumor immunity. analysis this process, together with MDV characterization, may help capture relationship development, mitochondrial quality control, inflammation. combination immune checkpoint inhibitors (i.e., atezolizumab bevacizumab) has approved as synergistic first-line treatment for unresectable or advanced lack biomarkers that allow prediction response and, therefore, patient selection, major unmet need. Herein, we overview linking dysfunction, pyroptosis, discuss how immunotherapy targets, at least partly, routes.

Language: Английский

Citations

3
Role of Extracellular Vesicles in the Progression of Brain Tumors DOI Creative Commons
Gabriella Schiera, Carlo Maria Di Liegro,

Francesco Vento

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(8), P. 586 - 586

Published: Aug. 2, 2024

Brain tumors, and, in particular, glioblastoma (GBM), are among the most aggressive forms of cancer. In spite advancement available therapies, both diagnosis and treatments still unable to ensure pathology-free survival GBM patients for more than 12–15 months. At basis poor ability cope with brain we can consider: (i) intra-tumor heterogeneity; (ii) heterogeneity tumor properties when compare different patients; (iii) blood–brain barrier (BBB), which makes difficult isolation tumor-specific biomarkers delivering therapeutic drugs brain. Recently, it is becoming increasingly clear that cancer cells release large amounts extracellular vesicles (EVs) transport metabolites, proteins, classes RNAs, DNA, lipids. These structures involved pathological process characterize any particular form Moreover, EVs able cross BBB directions. Starting from these observations, researchers now evaluating possibility use purified organic fluids (first all, blood saliva), order obtain, through non-invasive methods (liquid biopsy), biomarkers, perhaps, also obtaining nanocarriers targeted drugs.

Language: Английский

Citations

3
HSP90 N-terminal inhibition promotes mitochondria-derived vesicles related metastasis by reducing TFEB transcription via decreased HSP90AA1-HCFC1 interaction in liver cancer DOI

Lixia Liu,

Zhenming Zheng, Yaling Huang

et al.

Autophagy, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 26, 2024

Cancer cells compensate with increasing mitochondria-derived vesicles (MDVs) to maintain mitochondrial homeostasis, when canonical MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta)-mediated mitophagy is lacking. MDVs promote the transport of components into extracellular (EVs) and induce tumor metastasis. Although HSP90 (heat shock 90) chaperones hundreds client proteins its inhibitors suppress tumors, inhibitors-related chemotherapy unexpected Herein, we find that inhibitor causes damage but stimulates low LC3-induced release MDVs-derived EVs. However, why LC3 decreases what transcriptional regulatory mechanism formation under inhibition remain unknown. Because TFEB (transcription factor EB) most important transcription factor, HCFC1 (host cell C1) regulates

Language: Английский

Citations

3
Mitochondria-derived vesicles: potential nano-batteries to recharge the cellular powerhouse DOI Open Access
Shalini Mishra, Gagan Deep

Extracellular Vesicles and Circulating Nucleic Acids, Journal Year: 2024, Volume and Issue: 5(2), P. 271 - 275

Published: Jan. 1, 2024

Mitochondria dysfunction is increasingly recognized as a critical factor in various pathogenic processes. The mechanism governing mitochondrial quality control serves an adaptive response, ensuring the preservation of morphology, quantity, and overall function, crucial for cell survival. generation mitochondria-derived vesicles (MDVs) one processes control. Recent literature has suggested MDV heterogeneity; however, detailed characteristics subtypes still need to be studied better. studies have shown that MDVs also play role inter-organelle communication mitochondria besides For instance, Hazan et al. demonstrated functional from Saccharomyces cerevisiae release independent fission machinery. These vesicles, falling within typical size range MDVs, were selectively loaded with proteins, especially ATP synthase subunits. Intriguingly, these maintained membrane potential could generate ATP. Moreover, fuse naïve mitochondria, transferring their Lastly, this study revealed delivery ATP-producing presenting promising avenue rejuvenate ATP-deficient mitochondria. Overall, unveils novel by which maintaining cellular homeostasis important pathological conditions.

Language: Английский

Citations

2