bims-mitrat 2026-05-31 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–05–31
ten papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Mitochondrial transfer: A comprehensive analysis of mechanistic insights, preclinical applications, and technological innovations.
Intercellular Mitochondrial Transfer as Endogenous Neuroprotection: Mechanisms and Therapeutic Implications in Ischemic Stroke.
Mitochondrial Transfer-Driven Immune Evasion in the Tumor Microenvironment.
Mitochondrial transplantation protects the retinal pigment epithelial cells from the oxidative stress induced by NaIO3.
Mitochondrial transfer in sepsis: Dual role, mechanistic networks, and translational strategies.
Intramuscular mitochondria transplantation ameliorates paclitaxel-induced peripheral neuropathy by restoring neuronal mitochondrial homeostasis and function.
Dysfunction of the CD38-Miro1 Axis Disrupts Astrocyte-neuron Mitochondrial Transfer in Alzheimer's Disease: Mechanisms and Therapeutic Restoration.
Mitochondria-Associated mRNAs Restore ATP During Oxidative Stress via Cytosolic Translation.
Research Progress on How Multimodal Signals Regulate Neuronal Mitochondrial Homeostasis to Affect Diabetic Cognitive Impairment.
Light-Activated Isolation of High-Quality Mitochondria for Therapeutic Transplantation.

Neural Regen Res. 2026 May 14.

Mitochondrial transfer: A comprehensive analysis of mechanistic insights, preclinical applications, and technological innovations.

Yao Wang, Zitong Wang, Jie Zhao, Yimin Zhou, Dong Wei, Jingjing Zhao, Zhongqing Sun, Wen Jiang.

  Mitochondrial transfer, the intercellular exchange of functional mitochondria, is crucial for maintaining cellular homeostasis and promoting tissue repair, particularly in neurological disorders associated with mitochondrial dysfunction. This review addresses the mechanisms through which mitochondrial transfer occurs, including tunneling nanotubes, extracellular vesicles, gap junction channels, and cell fusion. Mitochondrial transfer and transplantation have demonstrated positive therapeutic effects in various disease models, such as cerebral hemorrhage, ischemic stroke, Alzheimer's disease, and multiple sclerosis. Exogenous mitochondria can integrate into recipient cells, enhancing adenosine triphosphate production, restoring redox balance, and improving cellular survival under stress conditions. However, clinical translation faces significant hurdles, including immune rejection, limited recipient cell uptake capacity, a lack of standardized manufacturing protocols, and unresolved ethical concerns regarding mitochondrial sourcing. To address these challenges, cutting-edge biotechnological strategies, such as mitochondrial surface modification, nanocarrier-based delivery, biomaterial-assisted transplantation, and the use of engineered vesicles, are being developed to enhance the precision, stability, and biocompatibility of mitochondrial delivery. Furthermore, innovative approaches, including CRISPR-based genome editing, 3D-bioprinted tissue models, and artificial intelligence-assisted predictive platforms, are being explored to enhance mitochondrial function and delivery efficiency. Current strategies to harness mitochondrial transfer include pharmacological agents that enhance mitochondrial dynamics, stem cell-based delivery of healthy mitochondria, and the aforementioned bioengineered platforms. In conclusion, the integration of mitochondrial transfer as a groundbreaking treatment option for neurological disorders relies on addressing two to three fundamental challenges. These include the establishment of standardized and scalable protocols for production and quality control, formulating approaches to minimize immune reactions and improve the efficiency of mitochondrial integration, and creating a well-defined ethical and regulatory framework for sourcing and utilizing mitochondria. The primary contribution of this work lies in its integrated analysis of mechanistic insights, preclinical applications, and technological innovations, providing a consolidated roadmap for advancing mitochondrial transplantation from bench to bedside.

Keywords:  artificial cells; biomaterial-assisted transplantation; extracellular vesicles; mesenchymal stem cells; mitochondrial dysfunction; mitochondrial surface modification; mitochondrial transfer; mitochondrial transplantation; neurological disorders; tunneling nanotubes

DOI:  https://doi.org/10.4103/NRR.NRR-D-25-01156
Transl Stroke Res. 2026 May 28. pii: 60. [Epub ahead of print]17(3):

Intercellular Mitochondrial Transfer as Endogenous Neuroprotection: Mechanisms and Therapeutic Implications in Ischemic Stroke.

Yun-Fan Zhang, Di Zhao, Jing-Jing Wei, Xiao Liang, Liu-Ding Wang, Jia-Wei Wang, Li-Bin Jiang, Ju-Ying Chen, Yun-Ling Zhang, Yue Liu.

  Ischemic stroke remains a leading cause of mortality and disability worldwide. Current reperfusion therapies are limited by narrow therapeutic time windows and the risk of secondary reperfusion injury, underscoring the urgent need for novel translatable neuroprotective targets. Mitochondrial dysfunction serves as a central hub in the ischemic cascade, contributing to energy failure, oxidative stress, calcium dysregulation, and various forms of programmed cell death. Recently, intercellular mitochondrial transfer has emerged as a crucial form of metabolic communication within the neurovascular unit (NVU). In the context of ischemia-reperfusion, donor cells can transfer functional mitochondria to compromised cells, facilitating metabolic rescue and remodeling the local microenvironment. Extensive in vivo and in vitro studies have shown that astrocytes, mesenchymal stem cells (MSCs), and pericytes can deliver mitochondria to neurons or brain microvascular endothelial cells (BMECs) through mechanisms such as tunneling nanotubes (TNTs), extracellular vesicles (EVs), and gap junctions. This transfer helps maintain blood-brain barrier (BBB) integrity and promotes neurological recovery. The process is finely regulated by inflammatory signaling, metabolic reprogramming, and epigenetic modulation, all of which influence the directionality and functional outcomes of the transfer. As a result, pharmacotherapies, non-pharmacological interventions, and direct mitochondrial transplantation have demonstrated considerable neuroprotective potential in experimental models and early-stage clinical research. However, challenges related to transfer selectivity, the durability of effects, delivery efficiency, and immune safety still hinder clinical translation. Future efforts must prioritize elucidating the underlying mechanisms, standardizing protocols, and developing precise stratification strategies to advance mitochondrial transfer-based interventions from proof-of-concept to a controllable and evaluable therapeutic option for stroke treatment.

Keywords:  Intercellular Mitochondrial Transfer; Ischemic Stroke; Mitochondrial Dysfunction; Mitochondrial Transplantation; Neuroprotection; Neurovascular Unit; Tunneling Nanotubes

DOI:  https://doi.org/10.1007/s12975-026-01446-5
Int Immunol. 2026 May 29. pii: dxag027. [Epub ahead of print]

Mitochondrial Transfer-Driven Immune Evasion in the Tumor Microenvironment.

Li Zhu, Yosuke Togashi.

  The tumor microenvironment (TME) is a complex landscape where metabolic interactions significantly dictate antitumor immunity. Immune evasion in cancer is typically discussed in terms of inhibitory receptors and ligands, suppressive cytokines, defective antigen presentation, and metabolic competition. However, recent evidence reveals that intercellular mitochondrial transfer adds a new mechanism of immune evasion in the TME. The mitochondrial fitness of T cells is central to sustained effector function, memory formation, and responsiveness to immune checkpoint blockade. Tumor cells can act as pathogenic mitochondrial donors, transferring functional or dysfunctional mitochondria to neighboring T cells via tunneling nanotubes and extracellular vesicles. This process involves a mitophagy imbalance that leads to the homoplasmic replacement of endogenous mitochondria, thereby driving T-cell senescence, impairing memory formation and long-term antitumor function, and ultimately weakening cancer immunosurveillance. Overall, mitochondrial transfer should be considered a new part of the tumor immune evasion framework. It also provides new therapeutic opportunities for improving cancer immunotherapy.

Keywords:  Mitochondrial transfer; T-cell exhaustion; immune checkpoint blockade; tumor-infiltrating lymphocytes

DOI:  https://doi.org/10.1093/intimm/dxag027
Exp Eye Res. 2026 May 27. pii: S0014-4835(26)00246-0. [Epub ahead of print]270 111090

Mitochondrial transplantation protects the retinal pigment epithelial cells from the oxidative stress induced by NaIO3.

Yeon-Jin Heo, Kausik Bishayee, Joo Yeon Jhun, Se Gyeong Han, Yeon Su Lee, Young Gun Park, Mi-La Cho, Yong Soo Park.

  The retinal pigment epithelium (RPE) is the outermost part of the retina, and it is essential for the photoreceptor survival and function. Oxidative stress, aging, accumulation of lipofuscin, and drusen can lead to retinal degenerative diseases such as age-related macular degeneration (AMD). Those stress conditions increase reactive oxygen species (ROS) levels and oxidative stress, which can induce mitochondrial dysfunction and promote RPE cell death during retinal degeneration. We transplanted mitochondria, isolated from C2C12 cells, into cultured RPE cells, and RPE cell injury was induced by NaIO3 treatment. To evaluate the protective effect of mitochondrial transplantation, Annexin V/PI and cell viability assays were performed to measure the cell survival, and ROS levels were measured by flow cytometry to analyze cellular stress. To understand the underlying protective mechanism of mitochondrial transplantation, we measure expression of the antioxidant genes, mitochondrial fusion/fission markers, and mitophagy makers using qRT-PCR and Western blot methods. Mitochondrial transplantation reduced NaIO3-induced cell death and ROS levels, and antioxidant genes related to the Nrf2 pathway were upregulated, providing a protective effect against retinal damage. In addition, mitochondrial fusion was increased, whereas fission was decreased in the NaIO3 model. Furthermore, mitophagy was increased by mitochondrial transplantation, which could clear damaged mitochondria through a cellular protective pathway. In conclusion, mitochondrial transplantation could protect the RPE cells by maintaining mitochondrial homeostasis and promoting the antioxidant pathway via Nrf2 activation. This study suggests that mitochondrial transplantation could be a potential treatment option for improving AMD progress in the future.

Keywords:  Mitochondrial transplantation; Mitophagy; Nrf2; ROS; Retinal pigment epithelium

DOI:  https://doi.org/10.1016/j.exer.2026.111090
Tissue Cell. 2026 May 22. pii: S0040-8166(26)00324-1. [Epub ahead of print]102 103631

Mitochondrial transfer in sepsis: Dual role, mechanistic networks, and translational strategies.

Yingyu Li, Yuhang Fan, Kangkai Wang, Nian Wang.

  Sepsis is a life-threatening clinical syndrome characterized by dysregulated host response, metabolic disturbance, and multiple organ dysfunction. Mitochondrial damage and bioenergetic failure are core pathological events driving sepsis progression. As a critical intercellular communication mechanism, mitochondrial transfer (MT) participates in mitochondrial quality control, energy homeostasis, and inflammatory regulation under septic stress. This review systematically summarizes the structural and functional mitochondrial injury in sepsis and endogenous quality control pathways. We focus on the four major MT routes, their crosstalk, and regulatory networks. The dual role of MT in sepsis is highlighted: functional MT supports tissue repair and organ protection, while damaged MT amplifies inflammation and exacerbates organ injury. We further outline current strategies to optimize MT-based therapy, including donor cell preconditioning, carrier engineering, and direct mitochondrial modification, as well as biosafety and translational challenges. This review provides an integrated theoretical framework and practical strategies for mitochondria-targeted interventions in sepsis.

Keywords:  Mitochondrial quality control; Mitochondrial transfer; Mitochondrial transplantation; Sepsis

DOI:  https://doi.org/10.1016/j.tice.2026.103631
Life Sci. 2026 May 22. pii: S0024-3205(26)00288-2. [Epub ahead of print]400 124479

Intramuscular mitochondria transplantation ameliorates paclitaxel-induced peripheral neuropathy by restoring neuronal mitochondrial homeostasis and function.

Sheng-Hua Wu, Ying-Chun Wang, Ching-Hsiang Ku, Shih-Ming Yang, Chen-Fuh Lam, Ming-Hong Tai, Shu-Hung Huang.

   AIMS: Paclitaxel-induced peripheral neuropathy (PIPN) is a significant, dose-limiting side effect of chemotherapy characterized by neuronal dysfunction stemming from mitochondrial damage. This study investigates the therapeutic potential of mitochondria transplantation for mitigating PIPN.
MATERIALS AND METHODS: PIPN was induced in rats via intraperitoneal paclitaxel injections (2 mg/kg, four doses). Allogeneic mitochondria from donor soleus muscles were injected into the vastus lateralis muscle of recipient rats. Sensory and motor functions were evaluated using behavioral tests. Mitochondrial biodistribution was tracked utilizing MitoTracker™ dye and lentiviral Mito-GFP labeling. Mechanistic evaluations included mitochondrial complex I-V activity assays, biogenesis marker quantification (TFAM, Nrf2), and histological assessments of sciatic nerve myelination, intraepidermal nerve fibers (IENFs), and neuromuscular junctions (NMJs).
KEY FINDINGS: Exogenous mitochondria successfully underwent retrograde transport from the muscle into the sciatic nerve and spinal cord, significantly alleviating paclitaxel-induced neuropathic pain and motor impairments. Mechanistically, transplantation restored mitochondrial complex activities and biogenesis markers in the peripheral nervous system, improved neuronal redox balance, and reduced microglial infiltration. Furthermore, mitochondrial transplantation promoted sciatic nerve remyelination and normalized target-tissue innervation by rescuing IENF and NMJ densities.
SIGNIFICANCE: Intramuscular mitochondria transplantation effectively counteracts paclitaxel-induced mitochondrial damage, suppresses neuroinflammation, and restores neuronal homeostasis, offering a promising therapeutic strategy for managing PIPN.

Keywords:  Chemotherapy-induced peripheral neuropathy; Mitochondria transplantation; Paclitaxel

DOI:  https://doi.org/10.1016/j.lfs.2026.124479
J Mol Neurosci. 2026 May 25. pii: 89. [Epub ahead of print]76(2):

Dysfunction of the CD38-Miro1 Axis Disrupts Astrocyte-neuron Mitochondrial Transfer in Alzheimer's Disease: Mechanisms and Therapeutic Restoration.

Ahmed M Abdelaziz, Mustafa M Shokr, Mohamed K Fathy, Mohamed N Fawzy.

  Alzheimer's disease (AD) is characterized by early bioenergetic failure, contributing to synaptic dysfunction and neuronal vulnerability. This review examines a critical compensatory mechanism, the transfer of functional mitochondria from astrocytes to neurons, and its profound failure in AD. We detail the coordinated molecular cascade of this mitochondrial shunt, initiated by neuronal distress signals that activate astrocytic CD38. CD38-generated cyclic ADP-ribose triggers calcium release, which then binds to the mitochondrial Rho GTPase Miro1, modulating mitochondrial trafficking and promoting peripheral positioning via kinesin motor complexes for intercellular transport through tunneling nanotubes (TNTs). Transient, localized Ca²⁺ signals bias mitochondria toward docking at the plasma membrane for export, whereas sustained pathologic Ca²⁺ overload impairs trafficking via motor disengagement and Miro1 dysfunction. In AD, this rescue pathway is catastrophically disrupted by NAD+ depletion, Aβ-induced calcium dysregulation, tau-mediated microtubule instability, and oxidative stress, leading to inhibited CD38 signaling, Miro1 dysfunction/impairment, and TNT dismantlement. We systematically explain how this multi-level impairment initiates a vicious cycle of bioenergetic collapse. We also look at promising treatment options that could help restore this shunt, such as NAD+ augmentation to reactivate CD38, Miro1 stabilizers to help with trafficking, and interventions to keep TNT intact. Targeting the astrocyte-neuron mitochondrial shunt may represent an innovative, disease-modifying strategy that could transform the therapeutic framework from simple protein clearance to the proactive restoration of intercellular metabolic support, offering a promising direction for next-generation AD therapeutics.

Keywords:  Alzheimer’s disease; Astrocyte; Bioenergetics; CD38; Calcium signaling; Miro1; Mitochondrial transfer; Neurodegeneration; Therapeutic target; Tunneling nanotubes

DOI:  https://doi.org/10.1007/s12031-026-02531-y
Antioxidants (Basel). 2026 May 03. pii: 580. [Epub ahead of print]15(5):

Mitochondria-Associated mRNAs Restore ATP During Oxidative Stress via Cytosolic Translation.

Dong-Bin Back, Gen Hamanaka, Ji-Hyun Park, Shin Ishikane, Masayoshi Tanaka, Takafumi Nakano, Yoshihiko Nakamura, Kazuhide Hayakawa.

  Mitochondrial transplantation has been proposed as a strategy to restore cellular bioenergetics after oxidative injury, but the mechanisms governing ATP recovery remain unclear. Using placental mitochondria, we examined ATP restoration following H2O2-induced oxidative stress. Unmodified mitochondria modestly increased ATP under baseline conditions but failed to restore ATP after injury. In contrast, lipid-coated mitochondria (MitoCoat) and lipid-encapsulated mitochondria-associated mRNAs (MitoCoat-mRNA) significantly increased ATP levels in injured cells. Transcriptomic analyses revealed that ATP recovery occurred without the normalization of canonical glycolytic or oxidative phosphorylation (OXPHOS) gene programs. Instead, unmodified mitochondria induced broad transcriptional responses associated with immune activation and cellular stress, whereas MitoCoat elicited a more restricted transcriptional profile. Notably, mitochondria-associated mRNAs alone restored ATP without detectable changes in host transcriptional programs. The removal of mitochondrial surface-associated ribosomes or the inhibition of cytosolic but not mitochondrial translation attenuated ATP recovery. The restoration of key metabolic enzymes through cytosolic translation, including PFKP, pyruvate dehydrogenase, and ATP synthase subunit ATP5A suggests that mitochondria-associated mRNAs promote recovery by re-establishing coupling between glycolysis and mitochondrial OXPHOS. Together, these findings identify encapsulated mitochondria-associated mRNAs as a potential strategy to restore cellular bioenergetics under oxidative stress.

Keywords:  MitoCoat; lipid modification; mRNA; mitochondria

DOI:  https://doi.org/10.3390/antiox15050580
J Integr Neurosci. 2026 May 19. 25(5): 45956

Research Progress on How Multimodal Signals Regulate Neuronal Mitochondrial Homeostasis to Affect Diabetic Cognitive Impairment.

Ying Li, Pengwei Zhuang.

  Diabetic cognitive impairment (DCI) affects approximately 25%-35% of patients with diabetes and is characterized by progressive cognitive decline. Dysfunction of mitochondria-the energy factories within neurons-is considered a potential pathogenic factor of DCI, involving processes such as oxidative stress, calcium overload, autophagic dysfunction, and genetic mutations, ultimately disrupting normal neuronal function. Maintaining mitochondrial quality and function is critical for neuronal health. Recent studies have shown that there are multiple ways in which cells can communicate signals, such as extracellular vesicles (EVs), tunneling nanotubes and gap junctions, which can repair and replace damaged mitochondria within receptor cells. Notably, EV-mediated mitochondrial transplantation has demonstrated significant potential by transferring healthy mitochondria to impaired neurons and restoring energy metabolism and antioxidant defences, thereby offering novel therapeutic strategies for intervening in DCI progression with valuable clinical translation potential. This review systematically elucidates multimodal signalling strategies targeting mitochondrial homeostasis, with a focused analysis on the role of EV-mediated mitochondrial transplantation in restoring neuronal energy balance, providing a theoretical foundation for the development of innovative DCI interventions.

Keywords:  cell communication; cognitive dysfunction; diabetes mellitus; mitochondria; neurons; type 2

DOI:  https://doi.org/10.31083/JIN45956
Angew Chem Int Ed Engl. 2026 May 28. e7935890

Light-Activated Isolation of High-Quality Mitochondria for Therapeutic Transplantation.

Hui Liu, Yuxin Jiao, Ting Zhang, Haiwei Wang, Yufei Xue, Jiayu Ding, Yang Ding, Meiling Wang, Weisen Zhang, Hua Bai, Bo Peng, Nicolas H Voelcker, Lin Li.

  Artificial mitochondrial transplantation (AMT) holds great promise for reprogramming cellular metabolism and restoring cell function. Its clinical translation, however, relies on access to mitochondria that are both of high purity and metabolically active, requirements that current isolation techniques struggle to meet. Conventional differential centrifugation (DC) method yields heterogeneous and low-activity mitochondria, whereas magnetic bead (MB)-based immuno-isolation leaves non-biodegradable beads permanently attached. Herein, we present a Light-Activated Mitochondrial Isolation (LAMI) platform comprising programmable mitochondria-targeting MBs and a photo-responsive release mechanism for the selective, efficient, and non-destructive extraction of high-quality mitochondria. LAMI employs magnetic nanoparticles decorated with a branched, modular probe architecture that supports systematic variation in mitochondria-targeting ligand type, ligand density, and optical tracking elements. Incorporation of a photo-cleavable linker allows on-demand, mild, and reagent-free release of captured mitochondria. Compared with DC method, LAMI produces mitochondria with markedly improved purity, structural integrity, and functionality. In an ischemia-reperfusion injury (IRI) model, LAMI-isolated mitochondria-based AMT exhibits superior therapeutic performance. Together, LAMI provides a non-destructive, efficient, and versatile mitochondrial isolation strategy that overcomes long-standing limitations of current methods, offering a robust platform to advance AMT and its future biomedical applications.

Keywords:  ischemia‐reperfusion injury; mitochondrial isolation; mitochondrial transplantation; multifunctional modular design; photo‐responsive release

DOI:  https://doi.org/10.1002/anie.7935890