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For example, circulating cell-free mitochondrial DNA (ccf-mtDNA) exists in multiple forms in the bloodstream, including naked mtDNA fragments, complexes bound to TFAM, fragments encapsulated within extracellular vesicles (EVs) or mitochondria-derived vesicles (MDVs), components of neutrophil extracellular traps (NETs), and a small proportion of intact mitochondria ( Notably, the previously described mechanisms whereby mtDNA leakage activates the cGAS–STING and NLRP3 inflammatory pathways may be systemically reflected by alterations in circulating ccf-mtDNA levels