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Figure 2. Patterns of mitochondrial transfer in cancer. (A-C) Mitochondrial transfer among cancer cells. (A) Chemoresistant TNBC cells transfer mitochondria to sensitive cancer cells by EVs; (B) Astrocyte tumors establish an interconnected network of TNTs and tumor microtubules and can transport mitochondria, which leads to increased tumor invasion and proliferation; (C) UV-induced stressed rat pheochromocytoma cells formed TNTs with normal cells and obtained transferred mitochondria that participate in the rescue effect; (D-F) Mitochondrial transfer between cancer and stromal cells. (D) MCF-7 breast cancer cells can internalize complete normal mitochondria and manifest as inhibition of cell proliferation; (E) Mitochondria extracted from MSCs to cancer cells result in an enhancement of OXPHOS activity that promotes the proliferative and invasive characteristics of recipient cancer cells. Inhibition of ICAM-1 blocks TNT formation, which promotes chemotherapy-induced cell death; Inhibition of PGC-1α in MSC suppresses mitochondrial transfer and impairs tumor cell proliferation; (F) CAFs transfer mitochondria to prostate cancer cells, further enhancing their metabolic and motile features; (G and H) Mitochondrial transfer between cancer and immune cells. (G) Mitochondrial transfer from T cells to cancer cells, facilitated by nanotubes, enhances the metabolic capabilities of the cancer cells while simultaneously depleting the immune cells; (H) M0 and M1 macrophages induced TNT network formation in PANC-1 cells, mitochondria delivered through TNTs. AIF: Apoptosis-inducing factor; CAF: cancer-associated fibroblast; ICAM-1: intercellular adhesion molecule-1; M0: M0-macrophage; M1: M1-macrophage; MSC: mesenchymal stem cell; mtDNA: mitochondrial deoxyribonucleic acid; OXPHOS: oxidative phosphorylation; PGC-1α: peroxisome-proliferator-activated receptor-gamma coactivator-1α; TNBC: triple-negative breast cancer; TNT: tunneling nanotube; EVs: extracellular vesicles; TNTs: tunneling nanotubes; UV: ultraviolet light.