An earlier study by Chiu et al.38 showed that the quantification of cir-mtDNA can be affected by applying different centrifugation speed and filtration protocols to the plasma of healthy individ- uals. This indicates that cir-mtDNA exists in various physical characteristics (free or particle-associated), as regards size and density. Further research has revealed that cir-mtDNA may be preponderantly (75.7%) associated with extracellular mitochondria, either in its free form or within large extracellular vesicles (EVs); to a lesser extent, it can also associate with other structures, notably small EVs ($18.4%) and exosomes or protein complexes ($5.9%).39 These findings point to the diversity of the circulating structures associated with cell-free DNA and to the high topological differences between cir-mtDNA and cir-nDNA. In addition, they confirm subsequent reports of the presence of circulating cell-free intact mitochondria.