July 17, 2025
A recent study published in Nature reveals that neurons associated with cancer can transfer their mitochondria to breast cancer cells, enhancing the cancer cells’ metabolism, energy production, and metastatic potential. This mitochondrial transfer occurs via specialized intercellular structures called tunneling nanotubes. The researchers used a novel genetic tool, MitoTRACER, to label and track cancer cells that received mitochondria, enabling detailed functional and molecular analysis. The transferred neuronal mitochondria “supercharge” the cancer cells, improving their survival, adaptability, and invasiveness. These insights suggest potential new therapeutic strategies targeting mitochondrial transfer pathways, though further validation in human models is needed.
Dr. Khasraw highlighted the clinical implications of the findings, suggesting potential therapeutic approaches (like tumor denervation or targeting mitochondrial transfer) and the need for further research to validate the mechanisms in human cancers. He also noted the limitations of current models and stressed the importance of cautious, rigorous clinical testing before translating these discoveries into treatments.
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Neurons Can Transfer Mitochondria to Cancer Cells
July 17, 2025; Karl Gruber
Cancer-associated neurons can transfer their mitochondria to cancer cells, boosting their metabolism and function. Mitochondria might also serve as a measure of risk of metastases. Future therapies could target these cells.
DOI:https://doi-org.proxy.lib.duke.edu/10.1158/2159-8290.CD-NW2025-0060
Cancer cells harness their increased mitochondrial content to boost their metabolism, growth, and invasive capacity.
Cancer-associated neurons can transfer mitochondria to cancer cells, boosting their metabolism and function. A recently published study provides the first evidence of this process in breast cancer cells, opening the door for studies exploring potentially new therapeutic targets (Nature 2025 Jun 25 [Epub ahead of print]).
In the study, researchers show that mitochondria are transferred through cell-to-cell communication, a process that requires specialized cellular structures. “Cancer-associated neurons actively transfer functional mitochondria to adjacent cancer cells through direct cell-to-cell contacts using intercellular structures called tunneling nanotubes,” says Simon Grelet, PhD, assistant professor of biochemistry and molecular biology at the University of South Alabama in Mobile, who co-led the study with Gustavo Ayala, MD, professor of pathology and vice chair for outreach at The University of Texas Health Science Center in Houston.
As a result, cancer cells gain various metabolic advantages, including enhanced oxidative phosphorylation and improved survival at distant metastatic sites, Grelet says. The secret behind this metabolic boost lies in the specialized nature of neuronal mitochondria.
“Neuronal mitochondria are uniquely adapted to sustain the high energy demands of the brain. By acquiring these exceptionally efficient neuronal mitochondria, cancer cells dramatically enhance their metabolic fitness, elevating oxidative phosphorylation capacity and ATP production,” Greletnotes. “This mitochondrial transfer effectively supercharges cancer cells—analogous to placing a high-performance muscle car engine into a regular car—conferring superior energy reserves [and] enhanced stress resilience and significantly boosting metastatic potential.”
As part of the study, researchers developed a novel genetic construct called MitoTRACER, designed to permanently label cancer cells that receive mitochondria from a genetically defined donor population and track their fate, Grelet explains. It employs a mitochondria-targeted tag protein expressed in donor cells that labels the cancer cells red. Once transferred to recipient cells, such as the breast cancer cells the researchers used, a reaction is triggered that permanently labels the cells green.
“This system uniquely enables us to distinguish naïve cancer cells from those that have received mitochondria, allowing for functional assays and omics-based analyses with high specificity. It also permits long-term lineage tracing to follow the fate of recipient cells and their descendants over time,” Grelet adds.
The findings highlight the importance of mitochondria in tumor biology, improving understanding of cancer plasticity and adaptation. Although it’s too soon to apply these findings to patient care, therapeutic strategies might one day target mitochondrial transfers to curb the metastatic capacity of cancer cells.
“Clinically, these findings suggest new therapeutic strategies, such as localized tumor denervation, inhibition of organelle transfer pathways, and metabolic vulnerability-based therapies,” says Mustafa Khasraw, MD, a physician–scientist and neuro-oncologist at Duke University School of Medicine in Durham, NC, and deputy director of the Center for Cancer Immunotherapy at the Duke Cancer Institute, who was not involved in the research. “Additionally, mitochondrial content near nerves may serve as a biomarker for metastatic risk, supporting the development of imaging and diagnostic tools.”
Grelet notes that future therapies could selectively target mitochondria-boosted cancer cells because they “may represent a vulnerable subpopulation that could be eliminated through precision therapies.”
But before any clinical applications can be developed, more research is essential. According to Khasraw, much of the data used in this study rely on in vitro systems and mouse xenograft models and may not fully represent human tumor–nerve interactions or the heterogeneity across cancer types and disease stages.
“The molecular signals for mitochondrial transfer will need to be better defined. Like any new promising therapeutic approach, the long-term consequences of disrupting mitochondrial transfer need to be tested in humans,” Khasraw says. Interventions, such as tumor denervation, although promising, “require rigorous clinical validation for safety [and] feasibility testing before any assessment of efficacy,” he adds.
Despite limitations, the study’s findings are likely to have a significant impact in oncology, linking cancer bioenergetics and neuroscience, says Hubert Hondermarck, PhD, a professor of biomedical sciences and head of the Cancer Neuroscience Laboratory at the University of Newcastle in Callaghan, New South Wales, Australia, who was not involved in the research. “This is new and big in terms of understanding the basic cellular and molecular mechanisms involved in cancer progression and metastasis, and particularly the role of the nervous system,” Hondermarck says.