Summary: When the brain’s “powerhouses”—mitochondria—fail, the result is often neurodegeneration, seen in diseases like Parkinson’s and Alzheimer’s. A breakthrough study has finally cracked the code on how cells take up and use “donated” mitochondria.
Researchers found that mesenchymal stromal cells (MSCs) actively “swallow” isolated, functional mitochondria through multiple cellular pathways. Once inside, these transplanted powerhouses don’t just sit there—they immediately boost the cell’s energy production, speed up repair, and protect against oxidative stress.
This discovery provides the scientific bedrock for a new field called Mitochondrial Therapy, which could revolutionize how we treat everything from strokes to aging.
Key Facts
- The “Transplant” Breakthrough: Functional mitochondria can be isolated from healthy cells and successfully delivered to compromised cells to restore energy levels (ATP production).
- Active Uptake: Cells don’t just passively absorb mitochondria; they use multiple “endocytic” pathways (clathrin, caveolin, and actin-dependent mechanisms) to actively bring them inside.
- Immediate Benefits: Once internalized, the new mitochondria increase cell proliferation, enhance antioxidant capacity, and boost maximal respiratory capacity.
- Non-Genetic Therapy: Unlike gene therapy, mitochondrial transplantation doesn’t change a cell’s DNA. It simply “refuels” the cell, making it a safer and faster option for acute injuries like heart attacks or strokes.
- Neuroprotective Potential: The researchers specifically noted that this therapy could be a game-changer for Parkinson’s and Alzheimer’s, where mitochondrial failure is a primary driver of cell death.
Source: Tokyo University of Science
Mitochondria, also known as the powerhouses of the cell, are essential for cell survival, repair, and adaptation. Not only do they generate most of the energy needed during a cell’s life, but they also regulate cell death, calcium balance, and responses to stress.
When mitochondria fail, which is a common feature of neurodegenerative diseases and many inflammatory and metabolic disorders, cells lose their ability to meet energy demands and maintain internal stability.
To tackle such problems, researchers are currently exploring therapies that aim to directly restore mitochondrial function.
A promising approach is mitochondrial transplantation, an emerging therapeutic concept in which functional mitochondria are isolated and delivered to compromised cells.
Despite growing interest and encouraging results in recent animal and cell-based studies, a fundamental problem has slowed progress in this field: scientists do not yet fully understand how transplanted mitochondria interact with recipient cells.
Do cells actively take up these organelles, or do mitochondria exert their effects from outside the cell? If mitochondria do enter cells, by what mechanisms do they cross the cell membrane, and do they remain functional once inside?
Without clear answers to these questions, it is difficult to optimize mitochondrial transplantation techniques, assess their safety and effectiveness, and ultimately use them in a clinical setting.
In a recent study, published in Volume 15 of Scientific Reports on December 29, 2025, a research team led by Associate Professor Kosuke Kusamori from the Department of Life Sciences and Pharmaceutical Sciences, Tokyo University of Science (TUS), Japan, directly addressed this knowledge gap.
They focused on mesenchymal stromal cells (MSCs), a type of cell widely studied in regenerative medicine, with significant biological properties and expanded therapeutic applicability.
Combining detailed biochemical measurements with multiple advanced imaging techniques, the team set out to determine if and how isolated mitochondria are taken up by MSCs, and whether these mitochondria remain biologically active after internalization.
This work was co-authored by fourth-year doctoral student Ms. Mai Kanai, fifth-year student Ms. Miyabi Goto, Dr. Shoko Itakura, and Dr. Makiya Nishikawa, all from TUS.
The researchers first isolated mitochondria from MSCs using a method designed to preserve their structural integrity. They confirmed that the isolated mitochondria were free of contamination by other cellular components and retained the ability to produce adenosine triphosphate (ATP). When these mitochondria were supplied to living cells, the team observed clear benefits.
Treated cells exhibited increased proliferation and were better able to withstand chemical and oxidative stress. Measurements of oxygen consumption—a standard way to assess mitochondrial respiration—revealed that the supplied mitochondria enhanced overall cellular energy metabolism.
“Mitochondrial treatment increased the respiration rate, ATP production rate, and maximal respiratory capacity of MSCs in a concentration-dependent manner. These findings suggest that the isolated mitochondria not only preserve their intrinsic bioenergetic activity but also exert proliferative and cytoprotective effects on MSCs and hepatocytes,” remarks Dr. Kusamori.
To determine whether these effects required the supplied mitochondria to actually enter the cells, the team tracked mitochondrial uptake over time.
Using fluorescence microscopy, confocal microscopy, flow cytometry, and label-free live imaging, they showed that mitochondria were gradually internalized by MSCs over several hours. Electron microscopy provided further confirmation, revealing mitochondria-like structures enclosed within membrane-bound vesicles inside the cells.
Then, by selectively blocking different endocytic pathways, the researchers demonstrated that MSCs rely on multiple endocytic mechanisms to internalize mitochondria, rather than a single dominant route.
Taken together, these findings shed light on the processes that drive mitochondrial uptake and how it can prove beneficial for cells.
“This study is an important achievement that provides a scientific foundation for the development of new therapies based on mitochondrial transplantation. We will pave the way for a new medical field called mitochondrial therapy, which directly supplements cellular energy functions and contributes to the realization of safer and more sustainable treatments,” concludes Dr. Kusamori.
These findings support mitochondrial-based therapy, though further research is needed before clinical use. Notably, understanding how mitochondria enter cells may allow researchers to enhance uptake efficiency and tailor delivery strategies to different cell types.
Unlike stem cell or gene therapy, mitochondrial transplantation does not change genetic identity; it restores bioenergetics by supplying functional organelles, offering a rapid option for acute or localized mitochondrial dysfunction.
Mitochondrial transplantation therapy could be especially valuable for conditions driven by mitochondrial dysfunction, such as toxin-induced liver injury, ischemia–reperfusion-related conditions caused by heart attack or stroke, and Parkinson’s and Alzheimer’s diseases.
More broadly, it may benefit ischemic tissue injury, neurodegenerative disorders, and age-related conditions in which mitochondrial activity is compromised.
Although many challenges remain before clinical translation, including confirming long-term safety and efficacy, controlling mitochondrial uptake and distribution in different tissues, avoiding unwanted immune responses, and ensuring the purity, consistency, and functional integrity of isolated mitochondria, this work puts us one step closer to a transformative therapeutic platform—one that holds much promise in next-generation regenerative medicine and anti-aging treatments.
Importantly, mitochondrial transplantation is still in the preclinical stage and requires years of further validation in disease models before human clinical trials can begin.
Key Questions Answered:
A: Yes! It’s an emerging field called “Mitochondrial Therapy.” Just as a car runs better with a new battery, a cell struggling with disease can be “jump-started” by injecting healthy, functional mitochondria. This study proves that the cells actually take these powerhouses inside and start using them immediately.
A: Most drugs treat the symptoms of neurodegeneration. Mitochondrial transplantation treats the cause—the loss of cellular energy. By restoring the power supply, we give neurons the energy they need to repair themselves and survive, potentially slowing down diseases like Parkinson’s or Alzheimer’s.
A: Because it uses naturally occurring organelles and doesn’t alter your genetic code (DNA), it is theoretically much safer than gene therapy. However, it’s still in the preclinical stage, and scientists are working on ensuring these “donated” powerhouses don’t trigger an immune response.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neurology research news
Author: Yoshimasa Iwasaki
Source: Tokyo University of Science
Contact: Yoshimasa Iwasaki – Tokyo University of Science
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Uptake mechanisms and functions of isolated mitochondria in mesenchymal stromal cells” by Mai Kanai, Miyabi Goto, Shoko Itakura, Makiya Nishikawa & Kosuke Kusamori. Scientific Reports
DOI:10.1038/s41598-025-28494-5
Abstract
Uptake mechanisms and functions of isolated mitochondria in mesenchymal stromal cells
Mitochondrial transplantation holds great promise as a therapeutic strategy; however, the mechanisms by which recipient cells interact with and internalize isolated mitochondria remain unclear.
Therefore, in this study, we isolated functional mitochondria from mesenchymal stromal cells (MSCs) and characterized their biological activities and physicochemical properties.
Additionally, effects of isolated mitochondria on MSC functions were evaluated. Treatment with isolated mitochondria promoted cell proliferation, improved cellular viability under stress conditions, and increased the oxygen consumption rate, indicating enhanced bioenergetic capacity.
Uptake of isolated mitochondria by MSCs was visualized via fluorescence imaging and quantitatively assessed over time, showing progressive internalization within 24 h. To investigate the mechanism of mitochondrial uptake, endocytosis was chemically inhibited, which revealed that endocytic pathways contributed to the internalization of the isolated mitochondria.
These findings suggest that MSCs incorporate isolated mitochondria via active uptake mechanisms and that the internalized mitochondria retain their functional activity.
Collectively, our results provide critical evidence of mitochondrial internalization in MSCs and offer insights into the potential applications of mitochondrial therapy for various diseases.
