Mitochondria are the power plants of the cell, vital to cell and tissue function. Mitochondria become damaged and dysfunctional with age, unfortunately, and this is thought to be a major contribution to age-related degeneration. That cells will take up mitochondria from the surrounding environment and put them to use has been established for some years. It is the basis for the development of mitochondrial transplantation therapies as a way to improve cell function in old tissues, delivering youthful mitochondria to augment the activities of native mitochondria that have been impaired by mechanisms of aging. Meanwhile, the research community continues to explore how exactly cells achieve uptake of mitochondria, as greater knowledge of the details may lead to ways to significantly improve on the coming first generation of mitochondrial transplantation therapies.
In today's open access paper, researchers report results from their study of how exactly the processes of endocytosis can be used to ingest mitochondria while preserving their structure and function. As a mitochondrion comes into contact with the exterior of the cell membrane, a region of the membrane wraps around the mitochondrion and then breaks off to bring it inside the cell, wrapped in an endosome. At some point the endosome is removed and the mitochondrion is fully internalized, intact and able to contribute to cell metabolism. This is a very high level description; there are a number of functionally distinct forms of endocytosis, and it appears that different types of endocytosis are used interchangeably for mitochondrial uptake, making it a more robust behavior.
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 hours. 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.
View the full article at FightAging
