Energy Crisis after Inter-System Mitochondria Transfer is the Direct Cause of Death by Sepsis

Abstract

Sepsis is one of the leading causes of death worldwide. With nearly 50 million incidences per year, it causes 11 million deaths worldwide annually, exceeding the 10 million total deaths caused by all tumors. Surprisingly, there is no specific drug available on market, explaining why it has a mortality rate as high as 22.5%. The lack of specific drug is mainly caused by the lack of understanding of how sepsis causes death. In this paper, I hypothesized that since energy production by mitochondria through respiration is not sustainable because the high level of reactive oxygen species (ROS) produced during respiration damages mitochondria themselves, mitochondria in the immune system cannot meet the dramatic and long-lasting high level of energy requirement of the system during sepsis. The immune system uses up all the functional mitochondria in the body by inter-system mitochondria transfer (ISMT), which dumps its used, unfunctional, or oxidized mitochondria to and recruits functional mitochondria from other systems. ISMT leads to the lack of functional mitochondria, hence energy, in the brain and the heart, and eventually causes death of the body. The hypothesis was supported by three key results: First, 2.5 hours after sepsis induction, mtDNA copy number increased dramatically in the spleen, brain, muscle, and blood, but decreased dramatically in the liver, kidneys, and skin. Second, mice died from sepsis showed a severe decline of mitochondria function in the brain and the heart. Finally, a single injection of isolated functional mitochondria to mice with sepsis reduced the mortality rate compared to mice received inactivated mitochondria.