Researchers from the University of California, Irvine have demonstrated that mitochondrial transplants can give cells a boost of energy and could potentially be the basis of therapies to address various cardiovascular, neurodegenerative, and metabolic diseases.
The mitochondria are the powerhouses of our cells, converting the nutrients we consume into energy to be used by every cell in our bodies. The mitochondria power the myriad of functions our cells must perform, which makes them essential for life. Unfortunately, as we age, some mitochondria can become damaged by free radical strikes, a consequence of both their location outside the cellular nucleus and the free radicals they produce as a side effect of energy production.
Damaged mitochondria tend to become dysfunctional and no longer efficient at producing energy, and their presence can be devastating in causing age-related diseases; this is why mitochondrial dysfunction is one of the hallmarks of aging.
The researchers of this new study wanted to see what would happen if they transplanted fresh mitochondria to cardiomyocytes (heart cells) and to determine if doing so could be the basis for a therapy that might help people with end-stage heart disease.
The idea for this experiment was inspired by the likely bacterial lineage of the mitochondria. Billions of years ago, the prokaryotic mitochondria are believed to have met our ancestors, the eukaryotes, and were absorbed into their cells. Even to this day, the mitochondria have separate DNA from our own, which is held in the cell nucleus; however, over time, mitochondria and cells have become increasingly bound together, and many of the mitochondrial genes have migrated to the nucleus. The researchers thought that given how our cells adopted mitochondria billions of years ago, it should be plausible to also transfer them into our cells in a direct, therapeutic way.
The research team isolated mitochondria and delivered them to the target cardiomyocytes using a transplant technique known as coincubation. They then waited for the mitochondria to settle into their new host cells before examining two important biomarkers of cellular metabolism: the oxygen consumption rate and the extracellular acidification rate. These biomarkers indicate how efficiently the cells are consuming and producing energy and are indicative of mitochondrial health and function. They took readings of these biomarkers at 2, 7, 14, and 28 days.
The results confirmed that cellular energy production increased in the cells two days following transplantation of the mitochondria and served to “supercharge” the cells for a while, although this boosted energy output declines over time.
The team experimented with transplanting mitochondria from different types of human cells into cardiomyocytes, and the results were similar. Perhaps most intriguingly, that the team tested transplanting mitochondria from rat cells to human cells, which also worked.
The next step for the research team will be to investigate if the transplanted mitochondria are adopted over the long term by the host cells.
Mitochondrial transplantation has been recently explored for treatment of very ill cardiac patients. However, little is known about the intracellular consequences of mitochondrial transplantation. This study aims to assess the bioenergetics consequences of mitochondrial transplantation into normal cardiomyocytes in the short and long term.
We first established the feasibility of autologous, non‐autologous, and interspecies mitochondrial transplantation. Then we quantitated the bioenergetics consequences of non‐autologous mitochondrial transplantation into cardiomyocytes up to 28 days using a Seahorse Extracellular Flux Analyzer. Compared with the control, we observed a statistically significant improvement in basal respiration and ATP production 2‐day post‐transplantation, accompanied by an increase in maximal respiration and spare respiratory capacity, although not statistically significantly. However, these initial improvements were short‐lived and the bioenergetics advantages return to the baseline level in subsequent time points.
This study shows for the first time that the transplanting of mitochondria from not just the patient’s own cells but other cells, from both humans and rats, leads to a short-term boost to cellular energy, effectively supercharging the cell for a short time. This has potential as a therapy in which a short-term increase of energy and performance could be useful, such as during repairs following damage to the heart.
However, while interesting, the effects of this last only a short while, perhaps as much as a week at best, so there is certainly room for improvement here. It also remains unclear how long the transplanted mitochondria function, if they are fully adopted by the host cells, and how long it takes before they fall foul of the same conditions that damaged the other mitochondria in the cell they joined.