Intracellular Consequences of Mitochondrial Transplantation

Mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells, which plays a vital role in cellular metabolism and homeostasis. As the powerhouse of the cell, the clinical manifestations of mitochondrial damage and dysfunction are devastating. While there has been much new interest and research on therapies involving mitochondria to mitigate diseases ranging from cancer and cardiovascular diseases to neurodegenerative diseases such as Parkinson and Alzheimer, the intracellular consequences of mitochondrial transplantation are not well-studied or well-understood. In this work, we show that autologous, non-autologus, and interspecies mitochondrial transplantation are feasible using a variety microscopy technique. Moreover, we show that non-autologous transplantation of healthy mitochondria from skeletal muscle cells into normal cardiomyocytes leads to improved bioenergetics acutely. Using a metabolic flux analyzer, we measured the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), after sequential treatment with Oligomycin, FCCP, Rotenone/Antimycin A post-transplantation, and compared the values to the control groups with no transplantation event at four time points of post 2-day, 7-day, 14-day , and 28-day. This was followed by mitochondrial genome sequencing studies to investigate whether transplanted mitochondria are truly adopted by the cell or not. This work delineates the potential of mitochondrial transplantation for clinical application in settings where there is an acute stress that would benefit from a boost in cellular bioenergetics. Given the observed bioenergetic profile of mitochondrial transplantation in normal cells, one of the remaining questions is whether the post-transplantation bioenergetics profile will be any different in cells with mitochondrial dysfunction. Future studies are crucial in determining the possible advantages of mitochondrial transplantation, if any, in mitigating mitochondrial diseases and other mitochondrial dysfunctions, as a cellular biotherapy