Fig. 5

Mitochondrial regulation of cellular interactions in the tumor microenvironment. Mitochondria play crucial roles in coordinating metabolic and immune responses within the tumor microenvironment. Different immune cell types exhibit unique metabolic adaptations: T cells shift between oxidative phosphorylation and glycolysis, macrophages polarize between pro- and antitumor states through metabolic switching, and NK cells maintain antitumor activity via specific metabolic pathways. Cancer-associated fibroblasts support tumor metabolism by providing metabolic resources and signaling molecules. These intricate mitochondria-mediated interactions regulate tumor progression, immune responses, and potential therapy resistance, highlighting the complex metabolic landscape of cancer microenvironments. β-catenin catenin beta, CAFs cancer-associated fibroblasts, CCL2 C-C motif chemokine ligand 2, cGAMP cyclic GMP-AMP, cGAS cyclic GMP-AMP synthase, DAMPs damage-associated molecular patterns, DRP1 dynamin-related protein 1, ETC electron transport chain, EVs extracellular vesicles, FAO fatty acid oxidation, HIF-1α hypoxia-inducible factor 1-alpha, IFN-γ interferon-gamma, IL-4/10 interleukin 4/10, MFN1/2 mitofusin 1/2, MMPs matrix metalloproteinases, mtDNA mitochondrial DNA, mtROS mitochondrial reactive oxygen species, NETs neutrophil extracellular traps, NF-κB nuclear factor kappa B, NK natural killer, OPA1 optic atrophy 1, OXPHOS oxidative phosphorylation, PGC-1α peroxisome proliferator-activated receptor-gamma coactivator 1-alpha, STING stimulator of interferon genes, TGF-β transforming growth factor-beta, Th17 T helper 17, TNF-α tumor necrosis factor-alpha, TNTs tunneling nanotubes, Treg regulatory T cell, type I IFN type I interferon. This figure was created with BioRender (https://biorender.com/)