Functional Mitochondrial Depletion in Non-cancer Cells Caused by Beneficial Mitochondria Exchange for Cancer Cells is the Direct Cause of Death by Cancer

Abstract The most important question for cancer is not how cancers form or how metastasis occurs, it is how metastatic cancer causes death. This paper proposed a theory to answer this question. Fast-proliferating cancer cells require more energy which is mainly produced by the respiration of mitochondria. However, respiration in mitochondria is not sustainable because the high level of reactive oxygen species (ROS) is produced during respiration and damages mitochondria through oxidization. As a result, to meet the long-lasting and high level of energy requirement, cancer cells use up their own mitochondria, and release the used, damaged, or oxidized mitochondria to, and acquire functional, undamaged, or unoxidized mitochondria from surrounding non-cancer cells. This beneficial mitochondria exchange for cancer cells is facilitated by metastasis, because metastatic foci are much smaller than the original tumor, providing a much larger contact surface between a given number of cancer cells and the surrounding non-cancer cells. The beneficial mitochondria exchange for cancer cells keeps repeating, and gradually leads to functional mitochondria depletion in non-cancer cells, most importantly in cells of vital organs such as the brain and the heart. As a result, it leads to a lack of energy in vital organs and eventually death of the patient. This theory was supported by three key results: First, mitochondria from the brain or heart of late-stage liver cancer or prostatic cancer mice showed decreased respiration rate; Second, metastatic liver cancer cells in the lung transfer their mitochondria to surrounding cells. Lastly, the administration of functional mitochondria to prostatic cancer mice increased their survival.