Horizontal mtDNA transfer between cells is common during mouse development

Cells transmit their genomes vertically to daughter cells during cell divisions. Here, we demonstrate the occurrence and extent of horizontal mitochondrial (mt)DNA acquisition between cells that are not in a parent-offspring relationship. Extensive single-cell sequencing from various tissues and organs of adult chimeric mice composed of cellr carrying distinct mtDNA haplotypes showed that a substantial fraction of cardiomyocytes, neurons, glia, intestinal, and spleen cells captured donor mtDNA at high levels. In addition, chimeras composed of cells with wild-type and mutant mtDNA exhibited increased trafficking of wild-type mtDNA to mutant cells, suggesting that horizontal mtDNA transfer may be a compensatory mechanism to restore compromised mitochondrial function. These findings establish the groundwork for further investigations to identify mtDNA donor cells and mechanisms of transfer that could be critical to the development of novel gene therapies.

Automated summary

Cells can acquire mitochondrial DNA (mtDNA) from other cells without a parent-offspring relationship, and this acquisition can occur at high levels. The transfer of mtDNA may serve as a compensatory mechanism to restore compromised mitochondrial function. These findings have important implications for understanding mtDNA transfer and developing gene therapies.