bims-mitrat 2026-06-28 papers

J Cereb Blood Flow Metab. 2026 Jun 25. 271678X261465848

EXPRESS: Intercellular Mitochondrial Transfer in Ischemic Stroke: Emerging Roles of Microglia.

Hong Yang, Xinyu Sun, Jie Jiang, Jinzhou Yu.

Mitochondrial dysfunction is a central driver of injury following cerebral ischemia-reperfusion, linking energy failure, oxidative stress, and inflammation. Intercellular mitochondrial transfer has been proposed as an adaptive mechanism to support metabolic homeostasis in the injured brain. While astrocyte-to-neuron transfer is supported by in vivo evidence, microglia-mediated transfer stays less well defined. Here, we review three proposed pathways: tunneling nanotube (TNT)-mediated transfer of intact mitochondria, extracellular vesicle (EV)-mediated transfer of mitochondrial components, and gap junction-associated signaling. TNT-mediated transfer is most closely associated with bioenergetic rescue, whereas EV-mediated processes primarily influence intercellular signaling. In parallel, mitochondrial damage-associated molecular patterns (DAMPs), including mitochondrial DNA, cardiolipin, and cytochrome c, can activate innate immune pathways and contribute to post-ischemic inflammation. The functional consequences of mitochondrial exchange vary according to donor-cell state, cargo integrity, and disease stage.

DOI: https://doi.org/10.1177/0271678X261465848

Trends Cancer. 2026 Jun 20. pii: S2405-8033(26)00126-3. [Epub ahead of print]

Horizontal mitochondrial transfer and the tug-of-war between cancer cells and immune cells.

Jaromir Novak, Denisa Hortova, Berwini Endaya, Magdalena Krulova, Michael V Berridge, Jiri Neuzil.

Horizontal mitochondrial transfer (HMT) is an emerging field of cell biology. Since its discovery, HMT has been extensively studied in the context of cancer due to the essential role of mitochondria in fueling the proliferation of tumor cells. The role of HMT in cancer, however, reaches far beyond a simple mechanism of organelle acquisition. Indeed, several recent studies have demonstrated HMT from cancer to immune cells and vice versa, with a profound impact on antitumor immune responses and potentially on immunotherapy efficacy. In this opinion article, we propose that HMT should receive attention as another modulatable mechanism of the functional tug-of-war between cancer and immune cells, further contributing to the complexity of the tumor microenvironment and likely sculpting the outcome of competition between the two teams of cells.

Keywords: horizontal mitochondrial transfer; immunotherapy; tumor-infiltrating lymphocytes; tunneling nanotubes

DOI: https://doi.org/10.1016/j.trecan.2026.05.008

Cells. 2026 Jun 17. pii: 1101. [Epub ahead of print]15(12):

Compensatory Intercellular Mitochondrial Transfer Improves Bioenergetics in P301L Tau-Affected Neuronal Cells.

Aurélien Riou, Aline Broeglin, Andreas Papassotiropoulos, Anne Eckert, Amandine Grimm.

Tauopathies are a group of neurodegenerative diseases characterized by the accumulation of abnormal tau protein, leading to mitochondrial dysfunction. Because of neurons' high energy demands, such impairments significantly contribute to neuronal vulnerability. Recent evidence indicates that mitochondria can be transferred between cells to support energy-deficient cells through intercellular mitochondrial transfer (IMT). Given the impact of pathological tau on mitochondrial transport and cytoskeletal dynamics, we hypothesized that IMT is altered in tauopathies. We investigated IMT from astrocytes to neurons, as well as the influence of abnormal tau protein on this process, using co-cultures of SH-SY5Y cells (neuronal model) and A172 cells (astrocytic model). Key data were then confirmed in human iPSC-derived neurons and astrocytes. We show that IMT is enhanced in the presence of abnormal tau and occurs predominantly through contact-dependent mechanisms. Transferred mitochondria were either integrated into the host mitochondrial network, degraded in lysosomes, or remained isolated in the recipient cells' cytosol. This transfer improved cellular respiration and was associated with increased bioenergetics in pathological cells. Together, our results highlight IMT as a link between tau pathology and neuronal metabolic adaptation, suggesting that this process reflects an endogenous metabolic adaptation holding therapeutic potential to mitigate energy deficits in neurodegenerative diseases.

Keywords: astrocytes; intercellular mitochondrial transfer; mitochondria; neurons; tauopathies

DOI: https://doi.org/10.3390/cells15121101

J Immunol. 2026 Jun 07. pii: vkag147. [Epub ahead of print]215(6):

Mechanisms and functions of intercellular mitochondria transfer to and from macrophages.

Wentong Jia, Jonathan R Brestoff.

Cell-to-cell communication is essential for maintaining homeostasis and coordinating complex biological processes in multicellular organisms. Classically, cells communicate using secreted peptides and metabolites and through cell contact-dependent signaling. Emerging studies over the past 20 years indicate that many cell types, including innate immune cells such as macrophages, participate in a process called intercellular mitochondria transfer, in which macrophages either donate their own mitochondria to other cells or accept mitochondria originating from another cell type. This raises the intriguing possibility that macrophages use mitochondria transfer as a mechanism of cell-to-cell communication. In this review, we describe the distinct mechanisms and functional roles of mitochondria transfer in macrophages across different organ systems and highlight how this biology contributes to health maintenance and disease pathogenesis.

Keywords: acceptor; cell-to-cell communication; donor; intercellular mitochondria transfer; macrophage

DOI: https://doi.org/10.1093/jimmun/vkag147

Sheng Wu Gong Cheng Xue Bao. 2026 May 25. pii: 1000-3061(2026)05-2246-15. [Epub ahead of print]42(5): 2246-2260

[Role and biochemical mechanism of exogenous mitochondria in alleviating glutamate-induced neuronal damage].

Zhihong Cui, Jingli Li, Peiyu Zhou, Dongyu Xiao, Ailing Fu.

The excessive concentration of glutamate in the brain is closely related to various neurological diseases, including neurodegenerative diseases, neuropsychiatric diseases, and epilepsy. It is a necessary approach to alleviate neuronal excitatory injury by regulating the glutamate concentration and inhibiting glutamate-induced cell death. To investigate whether mitochondrial transplantation could metabolize excessive glutamate, thereby reducing its neuronal excitatory injury, on the basis of previous research of our laboratory, this study used isolated liver mitochondria to reduce the glutamate level and increase the extracellular ATP content through the mitochondrial transplantation therapy, thereby rapidly inhibiting HT22 neuronal damage caused by glutamate. After the mitochondria kept acting on HT22 cells for 5 h, they could still reduce cellular oxidative stress levels, inhibit cell apoptosis, and improve the neuronal metabolic function. In the mouse model with prefrontal cortex injury caused by local injection of glutamate, the transplanted mitochondria repaired neuronal damage and alleviated abnormal symptoms in the open field test. In summary, this study reveals that transplanted mitochondria have pharmacological activity both in vitro and in vivo, providing a new idea for the treatment for neuronal excitatory injury-related diseases.

Keywords: energy metabolism; glutamate; mitochondrial therapy; neuronal excitatory injury

DOI: https://doi.org/10.13345/j.cjb.250643