Mitochondrial transfer — the active movement of mitochondria between cells — has emerged as a fundamental mechanism of intercellular communication with far-reaching implications for immune regulation, tissue homeostasis, and inflammatory disease. Once considered a phenomenon exclusive to artificial laboratory conditions, mitochondrial transfer is now recognised as a physiologically relevant process occurring across diverse immune and non-immune cell types, mediated by tunnelling nanotubes, extracellular vesicles, gap junctions, and cell fusion events.
In healthy immune physiology, mitochondrial transfer plays a critical role in supporting immune cell activation, metabolic reprogramming, and the resolution of inflammation. Donor cells — most notably mesenchymal stem cells — exert potent immunomodulatory effects in part through the donation of functional mitochondria to immune effector cells, restoring bioenergetics, reducing oxidative stress, and shaping the functional polarisation of recipient cells. This intercellular mitochondrial rescue has been documented in the context of macrophage polarisation, T-cell activation and exhaustion, dendritic cell function, and natural killer cell cytotoxicity, positioning mitochondrial transfer as a key axis of immune regulation.
In disease, dysregulation of mitochondrial transfer contributes to pathological immune outcomes across multiple conditions. In autoimmune and inflammatory disorders, aberrant horizontal mitochondrial transfer has been implicated in driving pro-inflammatory macrophage states, sustaining T-cell-mediated tissue damage, and disrupting immune tolerance. In the context of infection and sepsis, mitochondrial transfer between immune and stromal cells influences the resolution or persistence of inflammatory responses. Emerging evidence also links mitochondrial acquisition by tumour cells to immune evasion, through effects on immune cell exhaustion and the suppressive tumour microenvironment.
This Research Topic welcomes original research articles, reviews, and perspectives covering the immunological dimensions of mitochondrial transfer in both physiological and pathological contexts. Areas of interest include, but are not limited to: the molecular and structural mechanisms governing mitochondrial transfer between immune and non-immune cells; the role of mitochondrial transfer in immune cell activation, polarisation, and metabolic reprogramming; its contribution to autoimmune and inflammatory disease; its involvement in infection, sepsis, and innate immune responses; immune evasion mechanisms mediated by mitochondrial acquisition in cancer; and the therapeutic exploitation of mitochondrial transfer as an immunomodulatory strategy.
By bringing together research spanning immunology, cell biology, bioenergetics, and translational medicine, this collection aims to advance our understanding of mitochondrial transfer as a key regulator of immune responses — and its potential as a therapeutic target in inflammatory, autoimmune, and immune-mediated diseases.
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