The dynamic modifications in mitochondrial division and merging are pivotal in maintaining mitochondrial homeostasis and mtDNA distribution.260 Fission mediated by Drp1 induces the cytoplasmic stress of mtDNA, which promotes the release of CCL2 by HCC cells via activating the TLR9-mediated NF-B pathway, thereby facilitating M2-polarization and the recruitment of tumor-associated macrophages (TAMs).261 Moreover, blocking CCL2/CCR2 signaling by antagonists significantly reduces TAM invasion thereby restrains the advancement of HCC in orthotopic murine models. This evidence concerns the gene CCL2 and hepatocellular carcinoma.