bims-mitrat 2026-05-10 papers

Crit Rev Oncol Hematol. 2026 May 04. pii: S1040-8428(26)00243-X. [Epub ahead of print] 105356

Targeting the Mitochondrial Transfer Axis in Cancer: From Mechanistic Insights to Therapeutic Rewiring.

Shuai Ni, Zeng-Rong Xue, Yuan-Yuan Xin, Wei-Lin Jin.

Intercellular mitochondrial transfer is emerging as a therapeutic target in cancer. It drives a bidirectional metabolic-immune axis that fuels tumor progression and immune evasion. This review frames cancer as a rewired mitochondrial ecosystem. In this ecosystem, forward transfer (stroma→cancer) fuels proliferation and therapy resistance, while reverse transfer (cancer→immune) induces T-cell exhaustion. We highlight host metabolism (e.g., obesity) as a key modulator. Therapeutically, we chart a shift from inhibiting detrimental transfer (e.g., targeting Miro1/USP30) toward actively delivering functional mitochondria to immune cells. Integrating spatial multi-omics, AI, and advanced imaging will enable mitochondria-centric precision oncology. This approach moves beyond inhibition to active remodeling of the tumor microenvironment. This synthesis provides a pharmacological roadmap for targeting mitochondrial transfer to disrupt tumor-stroma-immune crosstalk and enhance therapeutic efficacy.

Keywords: Cancer immunotherapy; Extracellular vesicles; Intercellular communication; Metabolic-immune axis; Mitochondrial transfer; Targeted therapy; Tunneling nanotubes

DOI: https://doi.org/10.1016/j.critrevonc.2026.105356

Mol Cell Biochem. 2026 May 04.

Transplantation of Ru265-treated mitochondria enhances the therapeutic impact on skeletal muscle ischemia-reperfusion injury.

Saima Barki, Fazal Wahid, Shafia Khan, Laiba Tariq Abbasi, Zarrish Rubab, Ameer Hamza, Farman Ullah, Khadeeja Ahsan, Durre Shehwar, Muhammad Rizwan Alam.

Mitochondrial transplantation (MT) is a promising therapeutic approach for the treatment of several pathologies, including ischemia-reperfusion injury (IRI). However, its efficacy remains limited by the high calcium concentration of the transplantation milieu. Elevated extracellular calcium induces MCU-mediated matrix calcium overload, leading to the opening of the permeability transition pore and metabolic collapse of the transplanted organelles. We hypothesized that shielding mitochondria from the adverse effects of high calcium using the reversible MCU inhibitor, Ru265, would increase the efficacy of MT therapy. An acute, non-invasive hindlimb skeletal muscle IRI model was established in BALB/c mice using orthodontic rubber bands to mimic peripheral artery disease. Isolated liver mitochondria were treated with Ru265 and evaluated for their responsiveness to calcium using the mitochondrial swelling assay. Mice subjected to hindlimb IRI received either standard MT (Mitochondria alone) or Ru265-treated mitochondria (Mito + Ru), and treatment efficacy was evaluated using various parameters. IRI induced significant changes in mouse body weight, musculoskeletal dysfunction, systemic inflammation, lipid peroxidation, and skeletal muscle damage. While standard MT therapy provided baseline recovery, the Mito + Ru group demonstrated superior outcomes, including significant body weight recovery, reduced infarct size, and attenuated oxidative stress. Thus, reversible shielding of exogenous mitochondria from calcium stress using Ru265 enhances the efficacy of MT therapy in rodent skeletal muscle IRI.

Keywords: Ischemia Reperfusion Injury (IRI); Mitochondrial Calcium Uniporter (MCU); Mitochondrial Transplantation (MT); Ru265; Skeletal Muscle IRI

DOI: https://doi.org/10.1007/s11010-026-05563-5

Cell Metab. 2026 May 05. pii: S1550-4131(26)00143-9. [Epub ahead of print]38(5): 838-840

Special packaging enables effective mitochondrial delivery.

Caleb Jerred, Judith Hatzfeld, Alessandro Prigione.

Mitochondrial transplantation has emerged as a promising, though still experimental, strategy for treating mitochondria-related diseases. In a recent study in Cell, Du et al. demonstrate that packaging mitochondria within erythrocyte-derived plasma membranes enhances delivery efficiency and integration, thereby advancing the translational potential of this approach toward clinical application.

DOI: https://doi.org/10.1016/j.cmet.2026.04.005

Int J Mol Sci. 2026 Apr 09. pii: 3379. [Epub ahead of print]27(8):

Therapeutic Potential of Mitochondrial Transplantation with Focus on DBD.

Chen Guo, Chenwei Gu, Anjie Chen, Sixin Li, Si Shen, Zhonghao Tang, Jiandong Gui, Lijie Zhu, Sheng Wu, Yuanyuan Mi.

Diabetic Bladder Disease (DBD), a common urological complication of diabetes mellitus, severely compromises the quality of life of affected patients. Mitochondria, the primary energy-producing organelles in cells, are closely correlated with the pathogenesis and progression of DBD. As an emerging therapeutic modality, mitochondrial transplantation exhibits substantial potential for the management of DBD. This paper presents a comprehensive review of mitochondrial transplantation, with a focus on its fundamental theories, application conditions, safety profiles, and mitochondrial sources. Subsequently, we explore the association between mitochondrial dysfunction and the pathological mechanisms underlying DBD, analyze the disparities between mitochondrial transplantation and conventional therapeutic approaches, and discuss the prospects of combined and personalized treatment regimens. Finally, this review summarizes the ethical controversies surrounding this therapeutic strategy and outlines future research trends, aiming to lay a theoretical foundation for the development of novel therapeutic modalities against DBD.

Keywords: diabetic bladder disease; mitochondrial dysfunction; mitochondrial transplantation; oxidative stress

DOI: https://doi.org/10.3390/ijms27083379

Transpl Immunol. 2026 Apr 30. pii: S0966-3274(26)00048-1. [Epub ahead of print]96 102390

Nebulized mitochondrial transplantation attenuates inflammation and improves graft function in a murine donation after cardiac death lung transplant model.

Logan Langerude, Dianna Nord, Alexander McQuiston, Xinsheng Hu, Jennie Kwon, Satish Nadig, Jennifer Mulligan, Carl Atkinson, Zhenxiao Tu.

BACKGROUND: Mitochondrial transplantation is a promising therapy for ischemia reperfusion injury (IRI), with efficacy demonstrated in preclinical and early clinical cardiac studies. Its application in lung transplantation (LTx), particularly with donation after cardiac death (DCD) donors, remains unexplored. We hypothesized that nebulized delivery of mitochondria at the time of reperfusion would protect against IRI and engage mitochondrial quality-control pathways.
METHODS: A murine allogeneic orthotopic LTx model was used with DCD donor lungs subjected to 18 h of cold ischemia. At reperfusion, recipients received nebulized vehicle, Mitochondria-enriched fractions, or heat inactivated mitochondria-enriched fractions. At 24 h, graft oxygenation, histopathology, edema (wet-to-dry ratio, BAL albumin), and immune infiltration were assessed. BAL cytokines were measured by multiplex assay, mitochondrial uptake by flow cytometry, PINK1 expression, and circulating mitochondrial DNA (mtDNA) by qPCR.
RESULTS: Mitochondria-treated recipients had reduced histologic injury and improved graft function as determined by PaO₂ (p < 0.005). Edema was decreased (wet-to-dry 5.0 ± 0.4 vs 7.6 ± 1.1, p < 0.05), as was neutrophil infiltration (44.7 ± 2.2 vs 91.3 ± 8.0 MPO+ cells/image). BAL proinflammatory cytokines IL-6, KC, and MCP-1 were significantly reduced in recipients receiving mitochondrial therapy (p < 0.05). PINK1 expression was significantly increased in treated lungs, consistent with mitophagy activation. Serum mtDNA levels were unchanged between groups.
CONCLUSIONS: Nebulized mitochondrial transplantation improves oxygenation, reduces IRI, and activates PINK1-dependent quality control without increasing systemic mtDNA. This localized therapy represents a novel strategy to improve outcomes after DCD LTx.

Keywords: Donation after cardiac death; Ischemia reperfusion injury; Lung transplantation; Mitochondria

DOI: https://doi.org/10.1016/j.trim.2026.102390

Commun Biol. 2026 May 07.

Engrailed-1 potentiates mitochondrial transplant neuroprotection in spinal cord ischemia-reperfusion injury.

Wei Wang, Rui Tang, Shilun Gao, Xiaotian Han, Teng Shi, Tianxiang Gu, Enyi Shi.

Spinal cord ischemia-reperfusion injury (SCI/RI) triggers severe mitochondrial dysfunction and neuronal death. While mitochondrial transplantation (MT) is a promising strategy, its therapeutic potency remains limited. This study identifies the transcription factor Engrailed-1 (En-1) as a key regulator of mitochondrial homeostasis and a potential enhancer of MT. En-1 expression is significantly downregulated in SCI/RI models, whereas its restoration via hypoxic preconditioning or overexpression markedly improves neuronal survival. Mechanistically, En-1 stabilizes mitochondrial membrane potential, attenuates reactive oxygen species (ROS) production, and inhibits apoptosis by transcriptionally upregulating PDGFC. Mitochondria harvested from En-1-overexpressing cells (OE-En1-Mito) exhibit superior bioenergetic profiles and rapid neuronal uptake compared to unmodified mitochondria. In vitro, OE-En1-Mito increased ATP production and antioxidant activity; in vivo, transplantation preserved neuronal integrity and improved motor recovery in SCI/RI rats. Notably, silencing PDGFC in donor mitochondria abolished these neuroprotective benefits. Thus, En-1-modified MT provides superior neuroprotection for SCI/RI by leveraging the En-1/PDGFC axis.

DOI: https://doi.org/10.1038/s42003-026-10171-6