Abstract: It is generally assumed that somatic mtDNA mutations are originally created in the cells where these mutations are currently found. Accumulating data indicate, however, that cells with a particular mtDNA mutation tend to “cluster,” that is, occur repeatedly within a given sample, but not in the others. Clusters likely are clonal, which implies that mtDNA mutations do not originate in the cells that currently carry them, but rather in those cells' progenitors, such as stem or satellite cells, or even earlier in the development. Importantly, a majority of mtDNA mutations appear to belong to such clusters, and thus mutational events in progenitor cells may be one of the major sources of mtDNA mutations in healthy aging tissue. More research including the analysis of multiple samples per individual is needed to confirm the existence of clustering and to distinguish between the possible clustering mechanisms.