How cells preserve mitochondrial DNA quality across generations - Phys.org

A study conducted by researchers at Karolinska Institutet has uncovered how mammalian cells maintain mitochondrial DNA (mtDNA) integrity across generations. The research, published in Science Advances, highlights two primary mechanisms: a genetic bottleneck that selectively transmits mtDNA from mother to offspring, and purifying selection that eliminates harmful mutations during oocyte development. The findings demonstrate that a smaller mitochondrial bottleneck enhances genetic variation and allows for the effective removal of defective mtDNA, thereby reducing the transmission of harmful mutations. The researchers also noted that impairing mitochondrial recycling processes diminished this protective effect, leading to an accumulation of mutations and a decline in mtDNA quality. This research sheds light on how evolutionary processes keep mtDNA stable over time and suggests important biomedical implications, as mutations in mtDNA are associated with various diseases, including mitochondrial disorders, cancer, neurodegeneration, diabetes, and aging. By understanding these mechanisms, the study paves the way for potential therapeutic approaches to enhance mtDNA quality control and address conditions linked to mitochondrial genome instability.