EXAMINING THE ROLE OF MITOCHONDRIA IN IMMUNE RESPONSES: INFLAMMATION AND MACROPHAGE POLARIZATION

Abstract

Mitochondria play a crucial role in immune responses. Mutations in mitochondrial DNA(mtDNA) are associated with dysfunctional mitochondria, causing a series of downstream effects including increased mitochondrial reactive oxygen species (mROS) and release of mitochondria- related toxins such as mitochondrial damage-associated molecular patterns (mtDAMPs). One example is mitochondrial DNA (mtDNA), which results in inflammatory responses. However, the direct relationship between mtDNA mutation and dysfunction in cytokine production has not been characterized. In this study, we focused on elucidating the relationship between complex V disruption, which elicits mitochondrial permeability transition pore (mPTP) opening, and cytokine production. We found a decrease in cytokine expression levels upon blocking mPTP opening. Furthermore, we found that mitochondria dysfunction and subsequent cytokine production are associated with the polarization state of macrophages, the resident immune cells of the body in charge of inflammation and regeneration. In addition, we studied the direct effects of foreign mitochondrial internalization via mitoception on repolarization of macrophages and we observed an increase in M2 marker levels upon addition and internalization of donor mitochondria to recipient macrophages, supporting a direct effect of mitochondria on macrophage polarization.