Fig. 6

Pro and anti-inflammatory effects of mitochondrial transfer. Transferring mitochondria has both pro- and anti-inflammatory effects. For instance, A transferring MSC mitochondria to CD4 + T cells can reduce Th1 proliferation and IFN-γ production by inhibiting T-bet. Also, CD8 + T cells that adopt MSCs'mitochondria exhibit lower growth, IFNγ production, and cytotoxic activities due to the downregulation of T-bet and Eomes transcription factors. This action is mostly performed by the IP3-AKT-mTOR pathway and glycolysis suppression. Furthermore, MSCs deliver mitochondria to T cells, enhancing the expression of genes associated with Treg development and activation, such as FOXP3, CTLA-4, CD39, and CD73. B Cancer cells share mutant mtDNA and fragmented mitochondria with T and NK cells in the tumor microenvironment, causing NK mitochondrial and cytotoxicity malfunction, T cell exhaustion, and senescence. Regarding the pro-inflammatory effects of Mito T, C it has been suggested that MT enhances the activation and longevity of elderly human CD4 + T cells, D transferring of mitochondria isolated from hepatocytes to NK cells, resulting in a significant increase in proliferation and elevated secretion of cytotoxic granules including granzyme B, perforin and IFN-γ, (E) it seems that under metabolically stressed conditions, adipose tissue MQs utilize exogenous mitochondria to support aerobic respiration and thermogenesis toward a pro-inflammatory phenotype, F platelets can transfer mitochondria to neutrophils via EVs to enhance activation, adhesion, and migration potential as well as elevating intracellular calcium and ROS levels in neutrophils, G the Mito T from MQs undergoing pyroptosis into neutrophils leads to increased mtROS production, lower MMP and activation of the Gasdermin D axis, ultimately triggering NETs formation. MT; mitochondrial transfer, MSC; mesenchymal stem cells, IP3; inositol 1,4,5-trisphosphate, mTOR; mammalian target of rapamycin