Mitochondria Move Between Skin Cells to Fight Sun Damage and Speed Wound Repair

Mitochondria, the power-generating organelles that fuel nearly every complex cell, have long been viewed as strictly inherited possessions, passed down the maternal line and jealously guarded within each cell’s membrane. A new study challenges that picture for human skin. Researchers report that mitochondria can travel horizontally between the skin’s three principal resident cell types—melanocytes, keratinocytes, and fibroblasts—and that this traffic is not random. Instead, it follows a strikingly specific pattern, dominated by transfer from melanocytes to keratinocytes, and it intensifies when cells are hit by ultraviolet radiation, the very stressor that damages skin in the first place. The work, published in the Journal of Translational Medicine, also demonstrates that the same biology can be commandeered for therapy: isolated mitochondria, delivered artificially to damaged cells or applied directly to wounds, reduce oxidative stress, stimulate proliferation, and accelerate early tissue repair in both mouse and pig models.

The research team, led by Andrés Caicedo of Universidad San Francisco de Quito in Ecuador together with a broad international consortium, set out to answer a deceptively simple question: do skin cells share mitochondria with one another under normal conditions, and does that sharing change when the skin is under assault from sunlight? Horizontal mitochondrial transfer, or HMT, is an emerging form of intercellular communication that has been documented in other tissues, where stressed or damaged cells can receive functioning mitochondria from healthier neighbors, restoring their energy supply and improving their survival. But whether the cells of the epidermis and dermis engage in this exchange, and how it might relate to regenerative strategies built around mitochondria, remained poorly understood.

To find out, the investigators used a coculture system in which donor cells were labeled with MitoTracker Red, a fluorescent dye that stains active mitochondria, while recipient cells carried a green tag. When red-labeled organelles appeared inside green recipient cells, transfer had occurred, and fluorescence microscopy allowed the team to quantify how often it happened. The experiments were run in two configurations: direct two-dimensional coculture, in which donor and recipient cells physically touch, and transwell systems, in which a porous membrane separates the two populations while still allowing soluble factors to diffuse through. This design allowed the researchers to distinguish contact-dependent transfer from contact-independent mechanisms.

The results were unambiguous. Under basal conditions, transfer from melanocytes to keratinocytes was already the dominant route of exchange, and when the cells were exposed to ultraviolet radiation the transfer rate climbed dramatically, reaching approximately 39 percent of recipient keratinocytes in direct coculture. In transwell assays, where cells could not touch, the same donor–recipient pair transferred at less than 9 percent, indicating that the exchange relies overwhelmingly on direct cell-to-cell contact rather than on mitochondria or mitochondrial fragments drifting through the culture medium. Every other donor–recipient combination among the three skin cell types remained below 4 percent, and some pairs—melanocyte to melanocyte, keratinocyte to keratinocyte, melanocyte to fibroblast, and keratinocyte to melanocyte—showed no detectable transfer at all. Fibroblasts, notably, took up very few mitochondria from any source, whether from their own kind or from other skin cells, even after ultraviolet exposure.

That last observation may carry the most physiological weight. Keratinocytes, which form the outermost barrier of the skin and absorb much of the ultraviolet dose, appear to receive mitochondrial help precisely when they need it most, drawing functional organelles from melanocytes, the pigment-producing cells that sit alongside them in the basal epidermis. Fibroblasts, by contrast, live deeper in the dermis where ultraviolet penetration is weaker, but their apparent inability to import mitochondria suggests they may lack a stress-adaptation pathway available to their epidermal neighbors. The authors propose that this contact-dependent, cell-type-specific exchange represents a built-in resilience mechanism for the skin’s protective barrier, one that has gone unnoticed because it only operates at meaningful levels between particular cell pairs and under particular kinds of stress.

Having established that skin cells naturally share mitochondria, the team turned to the therapeutic question: can this process be exploited deliberately? The answer came in two stages. The first was artificial mitochondrial transfer, or AMT, performed in the laboratory. The researchers isolated mitochondria from three sources—human dermal fibroblasts, human Wharton’s jelly mesenchymal stem/stromal cells (WJ-MSCs) derived from umbilical cord tissue, and mouse bone marrow mesenchymal stem cells (BM-MSCs)—and delivered them to recipient fibroblasts. Before use, the isolated organelles were rigorously quality-controlled: scanning electron microscopy confirmed their structural integrity, tetramethylrhodamine methyl ester staining demonstrated that they retained an active membrane potential, and oxygraph measurements confirmed that they consumed oxygen and respired on substrates such as glutamate, pyruvate, and malate. These were not cellular debris but functioning bioenergetic machines.

When these stem-cell-derived mitochondria were delivered to fibroblasts, two clinically relevant effects emerged. First, WJ-MSC-derived mitochondria reduced the burst of reactive oxygen species, or ROS, that ultraviolet radiation normally triggers in skin cells, pointing to a direct antioxidant and protective function. Second, mitochondria from both human WJ-MSCs and mouse BM-MSCs significantly increased fibroblast proliferation, though the magnitude of the effect depended on the dose of mitochondria delivered, underscoring that dosing will be a critical parameter in any future clinical protocol. Fibroblasts are the workhorses of wound repair, producing collagen and rebuilding the dermal matrix, so a cell-free treatment that simultaneously lowers oxidative damage and boosts their proliferation could be valuable for burns, chronic wounds, and radiation-injured skin.

The second stage moved from the dish to living animals. In a murine model of primary-intention wound healing, the researchers applied mitochondria isolated from mouse BM-MSCs directly to the wounds. Histological analysis showed enhanced early tissue repair, and the effects were comparable to those achieved by administering the intact stem cells themselves—a remarkable result, because it suggests that at least part of the regenerative benefit of mesenchymal stem cell therapy can be reproduced by their mitochondria alone, without the cells. This has profound implications. Live stem cell therapies face hurdles of manufacturing complexity, immune compatibility, tumorigenicity concerns, and regulatory scrutiny; mitochondria are simpler, cannot replicate on their own, and could in principle be standardized, stored, and dosed like a conventional biologic.

To confirm the findings in a species whose skin more closely resembles our own, the team repeated the experiment in pigs, applying mitochondria derived from human Wharton’s jelly MSCs to primary-intention wounds. The outcomes were measured with a wound healing index, histological assessment of tissue organization, and spatial quantification of Ki67, a protein marker of actively dividing cells. Treated wounds showed a higher wound healing index, improved organization of collagen-containing tissue, and increased Ki67 positivity in both the epidermal and dermal regions directly involved in repair. In other words, the transplanted mitochondria appeared to wake up the local proliferative response on both sides of the skin’s architecture, driving new cell generation precisely where the healing front was advancing.

Taken together, the study draws a translational line between a naturally occurring behavior of skin cells and a new class of cell-free regenerative medicine. On one end, melanocytes appear to act as mitochondrial donors to keratinocytes under ultraviolet stress, a contact-dependent rescue mechanism that may help explain how skin tolerates lifelong sun exposure. On the other end, mitochondria isolated from mesenchymal stromal cells can be manufactured, applied to wounded tissue, and shown to accelerate healing across two mammalian species. The authors argue that this establishes a coherent biological rationale for mitochondria-based therapies in dermatology and wound care. Much work remains—optimal dosing, delivery vehicles, immunological considerations, and eventual human trials—but the conceptual advance is clear: the mitochondria that power our cells may one day be prescribed like medicine, harvested from stem cells and delivered to the skin to quench oxidative damage and rebuild what injury has destroyed.

Subject of Research: Horizontal mitochondrial transfer and mitochondrial transplantation for protection against ultraviolet radiation-induced damage and enhancement of skin wound healing

Article Title: Horizontal mitochondrial transfer and mitochondrial transplantation in skin: protection against UVR-induced ROS damage and enhancement of cell proliferation and wound healing

Article References: Horizontal mitochondrial transfer and mitochondrial transplantation in skin: protection against UVR-induced ROS damage and enhancement of cell proliferation and wound healing. (n.d.). https://doi.org/10.1186/s12967-026-08801-y

Image Credits: AI Generated

DOI: 10.1186/s12967-026-08801-y

Keywords: mitochondria, horizontal mitochondrial transfer, mitochondrial transplantation, skin, ultraviolet radiation, reactive oxygen species, mesenchymal stem cells, wound healing, keratinocytes, melanocytes, fibroblasts, regenerative medicine