bims-mitrat 2026-01-11 papers

Biosci Biotechnol Biochem. 2026 Jan 07. pii: zbag004. [Epub ahead of print]

Investigating interspecies mitochondrial transplantation on the malignancy of melanoma cells.

Fu-Chen Kuo, Bi-Ling Cheng, Ching-Chung Tsai, Ping-Chen Chen, Wei-Wen Sung, Kuen-Jang Tsai, Hsin-Yi Tsai, Yaw-Bin Huang, Chung-Jung Liu, Deng-Chyang Wu, Ming-Wei Lin, Bin Huang.

Transplanting allogeneic or even interspecies mitochondria to modulate cancer malignancy was investigated herein. Melanoma is a highly metastatic cancer that strongly relies on mitochondrial function. The mitochondrial membrane potential (MMP) and ATP of human (A375) and mouse (B16F10) melanoma cells, and four donor cells, human (HaCaT) and mouse (MPEK-BL6) keratinocytes, human (HUVEC) and mouse (MUVEC) endothelial cells were compared. The mitochondrial transplantations between mouse and human were identified. HUVEC mitochondria could uniquely retard the migration of B16F10. HUVEC mitochondria could be substantially transplanted into B16F10 and were colocalized with endogenous B16F10 mitochondria, in which, the branched mitochondria were converted into globular mitochondria. The reduced DRP1 and LC3 II corresponded to the reduced MMP and ATP. The decreased TGF-β, NANOG, SOX2, SMAD2/3, AKT, ERK, N-cadherin and MMP-9 corresponded to the attenuated invasion, elevated ROS and impaired cell viability. In conclusion, the feasibility of interspecies mitochondrial transplantation was preliminarily validated.

Keywords: B16F10; HUVEC; Interspecies; Melanoma; Mitochondrial transplantation

DOI: https://doi.org/10.1093/bbb/zbag004

Int J Mol Sci. 2025 Dec 28. pii: 332. [Epub ahead of print]27(1):

Mitochondrial Transplantation Restores Immune Cell Metabolism in Sepsis: A Metabolomics Study.

Tae Nyoung Chung, Se Rin Choi, Su-Hyun Kim, Choong Hwan Lee, Kyuseok Kim.

Sepsis induces severe immune and metabolic dysfunction driven by mitochondrial failure. Mitochondrial transplantation (MT) has emerged as a promising strategy to restore mitochondrial bioenergetics, but its metabolic impact on immune cells remains unclear. Here, we used gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics to evaluate metabolic alterations in peripheral blood mononuclear cells (PBMCs) and splenocytes from a rat polymicrobial sepsis model treated with MT. Principal component and partial least-squares discriminant analyses revealed distinct clustering between sham, sepsis, and MT groups. Sepsis markedly suppressed metabolites related to amino acid, carbohydrate, and lipid metabolism, including aspartic acid, glutamic acid, AMP, and myo-inositol, reflecting mitochondrial metabolic paralysis. MT partially restored these metabolites toward sham levels, reactivating tricarboxylic acid (TCA) cycle, nucleotide, and lipid pathways. Pathway analysis confirmed that exogenous mitochondria reversed sepsis-induced metabolic suppression and promoted bioenergetic recovery in immune cells. These findings provide direct metabolomic evidence that MT reprograms immune metabolism and restores oxidative and biosynthetic function during sepsis, supporting its potential as a mitochondrial-based metabolic therapy.

Keywords: energy metabolism; gas chromatography–mass spectrometry; immune cells; metabolomics; mitochondrial dysfunction; mitochondrial transplantation; oxidative phosphorylation; peripheral blood mononuclear cells; sepsis; splenocytes

DOI: https://doi.org/10.3390/ijms27010332

Platelets. 2026 Dec;37(1): 2610264

Assessing mitochondrial function and protein composition in platelet-derived extracellular vesicles.

Vanessa Veilleux, Nicolas Pichaud, Gilles A Robichaud, Luc H Boudreau.

Platelets, traditionally known for their role in hemostasis, also contribute to inflammation, cancer, and intercellular communication through the release of platelet-derived extracellular vesicles (or platelet-derived microparticles; PMPs). Among these vesicles, a subpopulation containing functional mitochondria, known as mitoMPs, can be transferred to recipient cells, thereby modulating their metabolism and biological responses. This mitochondrial transfer plays a key role in various pathological processes, where it may either restore metabolic functions or enhance cancer cell proliferation, survival, and metabolic plasticity. In this study, we developed a permeabilization protocol combined with high-resolution respirometry to assess mitochondrial respiration in both platelets and PMPs. First, we found that saponin was a more effective permeabilizing agent than digitonin to measure mitochondrial respiration in these models. Moreover, our analysis revealed distinct respiratory profiles between platelets and PMPs and demonstrated that freeze-thaw cycles severely compromise mitochondrial functions in PMPs. Additionally, we performed proteomic profiling of PMPs to characterize their protein cargo, which associate with specific molecular pathways, particularly those associated with mitochondrial metabolism. These results provide novel insights into the biological functions of PMPs and their potential involvement in disease processes. Together, these findings advance the understanding of PMP-mediated mitochondrial transfer and intercellular communication and establish a foundation for future biomedical and therapeutic investigations.

Keywords: High-resolution respirometry; OXPHOS; microparticles; mitochondria; platelets; proteomics

DOI: https://doi.org/10.1080/09537104.2025.2610264

Nature. 2026 Jan 07.

Mitochondrial transfer from glia to neurons protects against peripheral neuropathy.

Jing Xu, Yize Li, Charles Novak, Min Lee, Zihan Yan, Sangsu Bang, Aidan McGinnis, Sharat Chandra, Vivian Zhang, Wei He, Terry Lechler, Maria Pia Rodriguez Salazar, Cagla Eroglu, Matthew L Becker, Dmitry Velmeshev, Richard E Cheney, Ru-Rong Ji.

Primary sensory neurons in dorsal root ganglia (DRG) have long axons and a high demand for mitochondria, and mitochondrial dysfunction has been implicated in peripheral neuropathy after diabetes and chemotherapy1,2. However, the mechanisms by which primary sensory neurons maintain their mitochondrial supply remain unclear. Satellite glial cells (SGCs) in DRG encircle sensory neurons and regulate neuronal activity and pain3. Here we show that SGCs are capable of transferring mitochondria to DRG sensory neurons in vitro, ex vivo and in vivo by the formation of tunnelling nanotubes with SGC-derived myosin 10 (MYO10). Scanning and transmission electron microscopy revealed tunnelling nanotube-like ultrastructures between SGCs and sensory neurons in mouse and human DRG. Blockade of mitochondrial transfer in naive mice leads to nerve degeneration and neuropathic pain. Single-nucleus RNA sequencing and in situ hybridization revealed that MYO10 is highly expressed in human SGCs. Furthermore, SGCs from DRG of people with diabetes exhibit reduced MYO10 expression and mitochondrial transfer to neurons. Adoptive transfer of human SGCs into the mouse DRG provides MYO10-dependent protection against peripheral neuropathy. This study uncovers a previously unrecognized role of peripheral glia and provides insights into small fibre neuropathy in diabetes, offering new therapeutic strategies for the management of neuropathic pain.

DOI: https://doi.org/10.1038/s41586-025-09896-x