Mitochondrial Damage in Sepsis.

Mitochondria not only generate adenosine triphosphate (ATP) and act as the powerhouse of the cell but also contribute to host defense by producing reactive oxygen species. Therefore, mitochondrial damage in sepsis directly results in a shortage of energy currency and dysregulation of the immune system. Other than those, mitochondrial damage results in the release of highly dangerous mitochondrial DNA, facilitating acidosis by modulating the metabolism and inducing programmed cell death, thereby facilitating disease progression in sepsis. Various forms of cell death are induced by mitochondrial damage. Aponecrosis is a secondary conversion from apoptosis to necrosis. Although apoptosis is initially intended, it cannot be completed due to ATP depletion from mitochondrial damage, ultimately leading to inflammatory necrosis. Besides such accidental cell death, programmed inflammation-inducing cell deaths such as necroptosis, ferroptosis, and pyroptosis are induced by mitochondrial damage in sepsis. Based on these findings, the regulation of mitochondrial damage holds promise for the development of new therapeutic approaches for sepsis.