bims-mitrat 2025-05-18 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2025–05–18
seven papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute

Periprocedural therapeutics do not impair extracellular mitochondrial viability in transplantation.
Mitochondrial quality control and transfer communication in neurological disorders and neuroinflammation.
Mesenchymal stem cell-mediated mitochondrial transfer regulates the fate of B lymphocytes.
Mitochondrial transfer in endothelial cells and vascular health.
Astrocytic mitochondria modulate poststroke splenic immune responses, promote interleukin 10 production, and mediate neuroprotection after intracerebral hemorrhage.
Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components.
To transfer mitochondria or not to transfer mitochondria: ADP does the trick.

J Cereb Blood Flow Metab. 2025 May 14. 271678X251340232

Periprocedural therapeutics do not impair extracellular mitochondrial viability in transplantation.

Francisco Javier Miralles, Keiko Lynne Prijoles, Ashtyn Winter, Michael R Levitt, Yasemin Sancak, Melanie Walker.

  Mitochondrial transplantation is an emerging therapeutic approach for ischemia-reperfusion injury, offering the potential to restore cellular function through the engraftment of extracellular mitochondria. The successful clinical application of this strategy depends on the delivery of metabolically active mitochondria, yet the impact of circulating therapeutic agents on mitochondrial viability remains poorly understood. This study evaluates the effects of five clinically relevant agents commonly used during endovascular treatment of ischemic stroke-alteplase, cefazolin, lidocaine, phenylephrine, and heparinized saline-on extracellular mitochondria using an ex vivo model. Mitochondria were isolated from human skeletal muscle and mouse liver and exposed to these agents at clinically relevant and supra-physiological concentrations. Metabolic activity was assessed using a resazurin reduction assay as an indicator of mitochondrial viability. Even at concentrations up to 8-fold above clinical exposure, none of the agents significantly impaired mitochondrial function. These findings provide critical toxicological data demonstrating the compatibility of commonly used therapeutics with mitochondrial transplantation, supporting the development of safer and more optimized clinical protocols.

Keywords:  Drug toxicity; extracellular mitochondria; ischemia-reperfusion injury; mitochondrial transplantation; mitochondrial viability

DOI:  https://doi.org/10.1177/0271678X251340232
Front Immunol. 2025 ;16 1542369

Mitochondrial quality control and transfer communication in neurological disorders and neuroinflammation.

Yinrui Ma, Rui Song, Chenyang Duan.

  Mitochondria, as the primary energy factories of cells, play a pivotal role in maintaining nervous system function and regulating inflammatory responses. The balance of mitochondrial quality control is critical for neuronal health, and disruptions in this balance are often implicated in the pathogenesis of various neurological disorders. Mitochondrial dysfunction not only exacerbates energy deficits but also triggers neuroinflammation through the release of damage-associated molecular patterns (DAMPs), such as mitochondrial DNA (mtDNA) and reactive oxygen species (ROS). This review examines the mechanisms and recent advancements in mitochondrial quality control in neurological diseases, focusing on processes such as mitochondrial fusion and fission, mitophagy, biogenesis, and protein expression regulation. It further explores the role of mitochondrial dysfunction and subsequent inflammatory cascades in conditions such as ischemic and hemorrhagic stroke, neurodegenerative diseases and brain tumors. Additionally, emerging research highlights the significance of mitochondrial transfer mechanisms, particularly intercellular transfer between neurons and glial cells, as a potential strategy for mitigating inflammation and promoting cellular repair. This review provides insights into the molecular underpinnings of neuroinflammatory pathologies while underscoring the translational potential of targeting mitochondrial quality control for therapeutic development.

Keywords:  mitochondrial; mitochondrial quality control; mitochondrial transfer; neuroinflammation; neurological disorders

DOI:  https://doi.org/10.3389/fimmu.2025.1542369
Eur J Clin Invest. 2025 May 15. e70073

Mesenchymal stem cell-mediated mitochondrial transfer regulates the fate of B lymphocytes.

Veronika Somova, Natalie Jaborova, Bianka Porubska, Daniel Vasek, Natalie Fikarova, Martin Prevorovsky, Zuzana Nahacka, Jiri Neuzil, Magdalena Krulova.

   BACKGROUND: Mitochondrial transfer is becoming recognized as an important immunomodulatory mechanism used by mesenchymal stem cells (MSCs) to influence immune cells. While effects on T cells and macrophages have been documented, the influence on B cells remains unexplored. This study investigates the modulation of B lymphocyte fate by MSC-mediated mitochondrial transfer.
METHODS: MSCs labelled with MitoTracker dyes or derived from mito::mKate2 transgenic mice were co-cultured with splenocytes. Flow cytometry assessed mitochondrial transfer, reactive oxygen species (ROS) levels, apoptosis and mitophagy. Glucose uptake was measured using the 2-NBDG assay. RNA sequencing analysed gene expression changes in CD19+ mitochondria recipients and nonrecipients. Pathway analysis identified affected processes. In an LPS-induced inflammation model, mito::mKate2 MSCs were administered, and B cells from different organs were analysed for mitochondrial uptake and phenotypic changes. MSC-derived mitochondria were also isolated to confirm uptake by FACS-sorted CD19+ cells.
RESULTS: MSCs transferred mitochondria to CD19+ cells, though less than to other immune cells. Transfer correlated with ROS levels and mitophagy induction. Mitochondria were preferentially acquired by activated B cells, as indicated by increased CD69 expression and glycolytic activity. Bidirectional transfer occurred, with immune cells exchanging dysfunctional mitochondria for functional ones. CD19+ recipients exhibited increased viability, proliferation and altered gene expression, with upregulated cell division genes and downregulated antigen presentation genes. In vivo, mitochondrial acquisition reduced B cell activation and inflammatory cytokine production. Pre-sorted B cells also acquired isolated mitochondria, exhibiting a similar anti-inflammatory phenotype.
CONCLUSIONS: These findings highlight mitochondrial trafficking as a key MSC-immune cell interaction mechanism with immunomodulatory therapeutic potential.

Keywords:  B cell; immunoregulation; mesenchymal stem cell; metabolism; mitochondria

DOI:  https://doi.org/10.1111/eci.70073
Trends Cell Biol. 2025 May 13. pii: S0962-8924(25)00105-9. [Epub ahead of print]

Mitochondrial transfer in endothelial cells and vascular health.

Gwang-Bum Im, Juan M Melero-Martin.

  Mitochondria play a vital role in cellular energy metabolism and vascular health, with their function directly influencing endothelial cell (EC) bioenergetics and integrity. Mitochondrial transfer has emerged as a key mechanism of intercellular communication, impacting angiogenesis, tissue repair, and cellular homeostasis. This review highlights recent findings on mitochondrial transfer, including natural mechanisms - such as tunneling nanotubes (TNTs) and extracellular vesicles (EVs) - and artificial approaches like mitochondrial transplantation. These processes enhance EC function and support vascularization under pathological conditions, including ischemia. While early clinical trials demonstrate therapeutic potential, challenges such as mitochondrial instability and scaling host-derived mitochondria persist. Continued research is essential to optimize mitochondrial transfer and advance its application as a therapeutic strategy for restoring vascular health.

Keywords:  angiogenesis; endothelial cells; mitochondrial transfer; mitochondrial transplantation; vascular regeneration

DOI:  https://doi.org/10.1016/j.tcb.2025.04.004
Neuroreport. 2025 May 13.

Astrocytic mitochondria modulate poststroke splenic immune responses, promote interleukin 10 production, and mediate neuroprotection after intracerebral hemorrhage.

Ryosuke Tashiro, Yuki Kitamura, Jesus Bautista-Garrido, Guanghua Sun, Gab Seok Kim, Jaroslaw Aronowski, Joo Eun Jung.

  We recently demonstrated that systemically transplanted astrocytic mitochondria enter the intracerebral hemorrhage (ICH)-affected brain, where they protect the neurons by mitigating oxidative damage via upregulation of the manganese superoxide dismutase (Mn-SOD), ultimately contributing to functional recovery after ICH in mice. Although our previous study clearly demonstrated the beneficial effects of mitochondria within the brain, the effect of transferred mitochondria on the peripheral system was not yet studied. Thus, here, we studied the impact of astrocytic mitochondria transfer on post-ICH recovery and modulation of systemic immune responses. We used the autologous blood injection model for the mouse ICH surgery. Mice subjected to ICH received astrocytic mitochondria intravenously at 1 h, 7, and 14 days post-ICH onset, and the splenic immune responses of these mice were analyzed at 21 days. An ICH-like injury was induced in vitro using primary cultured neurons treated with recombinant interleukin-10, and cell viability, reactive oxygen species levels, and gene expressions were analyzed. We demonstrate that systemic transplantation of astrocytic mitochondria increases the population of splenic B cells, production of interleukin-10 by B cells, and plasma interleukin-10 levels in mice after ICH. Furthermore, in the ICH-like injury in vitro, exogenous interleukin-10 (to model spleen-mediated interleukin-10 increase) upregulated Mn-SOD expression in the cultured neurons and promoted neuronal survival and neuroplasticity-related gene expressions, suggesting interleukin-10 role in cytoprotection and repair/recovery under ICH-like condition. Thus, systemic transfer of astrocytic mitochondria modulates post-ICH peripheral immune responses, which may participate in functional recovery.

Keywords:  B cells; ICH; astrocytes; interleukin-10; mitochondria; spleen

DOI:  https://doi.org/10.1097/WNR.0000000000002175
J Cereb Blood Flow Metab. 2025 May 14. 271678X251338971

Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components.

Mingjin Wang, Weida Wang, Michael Chopp, Zheng Gang Zhang, Yi Zhang.

  Extracellular vesicles (EVs) facilitate the transfer of biological materials between cells throughout the body. Mitochondria, membrane-bound organelles present in the cytoplasm of nearly all eukaryotic cells, are vital for energy production and cellular homeostasis. Recent studies highlight the critical role of the transport of diverse mitochondrial content, such as mitochondrial DNA (mt-DNA), mitochondrial RNA (mt-RNA), mitochondrial proteins (mt-Prots), and intact mitochondria by small EVs (<200 nm) and large EVs (>200 nm) to recipient cells, where these cargos contribute to cellular and mitochondrial homeostasis. The interplay between EVs and mitochondrial components has significant implications for health, metabolic regulation, and potential as biomarkers. Despite advancements, the mechanisms governing EV-mitochondria crosstalk and the regulatory effect of mitochondrial EVs remain poorly understood. This review explores the roles of EVs and their mitochondrial cargos in health and disease, examines potential mechanisms underlying their interactions, and emphasizes the therapeutic potential of EVs for neurological and systemic conditions associated with mitochondrial dysfunction.

Keywords:  Extracellular vesicles; energy metabolism; mitochondria; mitochondrial components

DOI:  https://doi.org/10.1177/0271678X251338971
PLoS Biol. 2024 Aug;22(8): e3002754

To transfer mitochondria or not to transfer mitochondria: ADP does the trick.

Jaromir Novak, Jiri Neuzil.

Horizontal mitochondrial transfer (HMT) has emerged as a novel phenomenon in cell biology, but it is unclear how this process of intercellular movement of mitochondria is regulated. A new study in PLOS Biology reports that ADP released by stressed cells is a signal that triggers HMT.

DOI: https://doi.org/10.1371/journal.pbio.3002754