bims-mitrat 2025-08-10 papers

Ageing Res Rev. 2025 Aug 05. pii: S1568-1637(25)00202-8. [Epub ahead of print]112 102856

Strategies to rescue mitochondria in Parkinson's disease: The significance of mitochondrial transfer.

Junhan Liang, Zhaoqin Su, Gongmeiyue Su, Madiha Rasheed, Shiyi Tang, Hafsa Sunniya, Mohamed Maazouzi, Yaoyuan Cui, Junxiao Wang, Xuezhe Wang, Jing Yang, Mingchao Ding, Zhao Li, Yulin Deng.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuronal degeneration and pathological α-synuclein accumulation. Mitochondrial dysfunction is a central feature in PD pathogenesis, contributing to impaired bioenergetics, oxidative stress, neuroinflammation, and defective organelle communication. This review synthesizes the current understanding of mitochondrial quality control mechanisms, including fission, fusion, mitophagy, and biogenesis, and their disruption in PD. Particular emphasis is placed on the role of intercellular mitochondrial transfer as a compensatory mechanism. Emerging evidence suggests that mitochondria can be transferred between neurons and glial cells through tunneling nanotubes, extracellular vesicles, and gap junctions, offering protective effects by restoring metabolic function and attenuating cellular stress. We examine the molecular mediators of these transfer pathways, the influence of PD-associated mutations, and the bidirectional dynamics between donor and recipient cells. Additionally, we explore translational strategies, including mitochondrial transplantation, bioengineered mitochondria, and stem cell-based delivery systems. While preclinical models demonstrate promising therapeutic outcomes, clinical translation faces challenges, including targeting specificity, mitochondrial viability, and immune compatibility. By integrating mechanistic insights with therapeutic developments, this review highlights mitochondrial transfer as a novel and promising approach in the future treatment of PD, potentially addressing longstanding limitations in conventional neuroprotective strategies.

Keywords: Future therapies; Mitochondria transfer; Mitochondrial dysfunction; Parkinson’s disease; Quality control

DOI: https://doi.org/10.1016/j.arr.2025.102856

Front Immunol. 2025 ;16 1625814

Unveiling mitochondrial transfer in tumor immune evasion: mechanisms, challenges, and clinical implications.

Ruoyan Liu, Wenhui Shan, Zhening Wang, Hong Wang, Chunyan Li, Lei Yang, Rui Guo.

Background: Mitochondrial transfer, the intercellular transmission of mitochondria via tunneling nanotubes(TNTs), extracellular vesicles(Evs), or cell fusion, has emerged as a critical mechanism in cancer progression. Increasing evidence suggests that this phenomenon not only supports tumor cell metabolism and drug resistance but also contributes to immune evasion, a hallmark of cancer.
Objective: This study aims to systematically explore the intellectual structure, research hotspots, and emerging trends of mitochondrial transfer in tumor immune evasion using bibliometric and visualization tools.
Method: Publications from 2003 to 2025 were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were used to analyze annual outputs, co-occurring keywords, citation bursts, clustering patterns, and co-cited references.
Results: A total of 124 records were analyzed. The number of publications increased sharply after 2017, indicating growing research interest. Key terms such as "tunneling nanotubes," "mitochondrial transfer," and "immune escape" were frequently co-mentioned. Although "immune escape" is retained here to reflect the exact terminology used in the bibliometric database (Web of Science Core Collection), the manuscript text consistently adopts the term "immune evasion" for conceptual clarity and terminological standardization. Timeline cluster analysis identified several sustained hotspots, including acute myeloid leukemia (AML), stromal cells, and the cancer microenvironment. Citation burst analysis revealed emerging attention toward "expression," "stem cells," and "tumor microenvironment" in recent years.
Conclusion: Mitochondrial transfer has transitioned from a structural phenomenon to a key immunological modulator in cancer. This bibliometric analysis highlights its central role in immune evasion and identifies future research directions for therapeutic exploitation.

Keywords: bibliometric analysis; immunology; mitochondrial transfer; tumor immune evasion; tumor microenvironment

DOI: https://doi.org/10.3389/fimmu.2025.1625814

PLoS One. 2025 ;20(8): e0329672

Adipose-derived mesenchymal stem cells and retinal pigment epithelial cells interactions in a stress environment via tunneling nanotubes.

Merve Gozel, Karya Senkoylu, Cem Kesim, Murat Hasanreisoglu.

This study aims to demonstrate the formation of tunneling tubes (TNTs) between adipose-derived mesenchymal stem cells (AdMSCs) and retinal pigment epithelial cells (RPE-1) and their alterations in response to experimental stress conditions. Serum starvation was employed as a stress condition to induce TNTs between the AdMSC and RPE-1 cells. The presence of TNTs was demonstrated through immunofluorescence microscopy, while scanning electron microscopy was utilized to determine the average thickness. Cell viability was assessed after stress by CellTiter-Glo, and H2DCFH-DA probes evaluated the cells' reactive oxygen species (ROS) levels. Further, JC-1 labelled mitochondrial exchange between cells via TNTs was confirmed by time-lapse imaging. A transmembrane culture system was employed to inhibit TNTs. In this study, we investigated the role of TNTs in facilitating intercellular communication and mitochondrial transfer between AdMSCs and RPE-1 cells under stress. We found that TNT-mediated mitochondrial transfer from AdMSCs to RPE-1 helps to reduce ROS levels and improve cell viability. We demonstrated that direct interaction between AdMSCs and RPE-1 cells was crucial for stress recovery. Co-culture enhanced the viability and sustained the RPE-1 cells' function after stress-induced damage. Mechanical inhibition of TNT formation decreased cell viability and elevated ROS levels, indicating the importance of TNTs in cellular protection. The findings can provide a new perspective on the therapeutic potential of stem cell-based therapy in protecting retinal pigment epithelium cells against stress-induced damage and promoting tissue regeneration.

DOI: https://doi.org/10.1371/journal.pone.0329672

bioRxiv. 2025 Aug 01. pii: 2025.08.01.668058. [Epub ahead of print]

Differential Bioenergetic Profile of Human Glioblastoma following Transplantation of Myocyte-derived Mitochondria.

Kent L Marshall, Ethan Meadows, Alan Mizener, John M Hollander, Christopher P Cifarelli.

Glioblastoma (GBM) exhibits profound plasticity, enabling adaptation to fluctuating microenvironmental stressors such as hypoxia and nutrient deprivation. However, this metabolic rewiring also creates subtype-specific vulnerabilities that may be exploited therapeutically. Here, we investigate whether mitochondrial transplantation using non-neoplastic, human myocyte-derived mitochondria alters the metabolic architecture of GBM cells and modulates their response to ionizing radiation. Using a cell-penetrating peptide-mediated delivery system, we successfully introduced mitochondria into two mesenchymal-subtype GBM cell lines, U3035 and U3046. Transplanted cells exhibited enhanced mitochondrial polarization and respiratory function, particularly in the metabolically flexible U3035 line. Bioenergetic profiling revealed significant increases in basal respiration, spare respiratory capacity, and glycolytic reserve in U3035 cells post-transplantation, whereas U3046 cells showed minimal bioenergetic augmentation. Transcriptomic analyses using oxidative phosphorylation (OXPHOS) and glycolysis gene sets confirmed these functional findings. At baseline, U3035 cells expressed high levels of both glycolytic and OXPHOS genes, while U3046 cells were metabolically suppressed. Following radiation, U3035 cells downregulated key OXPHOS and glycolysis genes, suggesting metabolic collapse. In contrast, U3046 cells transcriptionally upregulated both pathways, indicating compensatory adaptation. These results identify and establish mitochondrial transplantation as a metabolic priming strategy that sensitizes adaptable GBM subtypes like U3035 to therapeutic stress by inducing bioenergetic overextension. Conversely, rigid subtypes like U3046 may require inhibition of post-radiation metabolic compensation for effective targeting. Our findings support a novel stratified approach to GBM treatment which integrates metabolic subtype profiling with bioenergetic modulation.

DOI: https://doi.org/10.1101/2025.08.01.668058