Assessing the Spread of Mitochondrial Mutations in Tissue

There is evidence for mitochondrial DNA mutations to spread throughout a tissue, though the degree to which each of the possible mechanisms contribute to this outcome is unknown. Mitochondrial DNA mutations in stem cells will spread in the same way as nuclear DNA mutation, producing mosaicism. Cells can also transfer mitochondria, however. Further, mitochondria are subject to selection effects based on their continued replication and removal by quality control mechanisms. Thus it is far from clear as to exactly how any observed snapshot of mitochondrial mutations came about. Researchers have taken a swing at this challenge, as noted here, but pay much more attention to substitutions than to deletions that completely disable mitochondrial genes. We might expect that deletions are the more important form of mutation. Nonetheless, the researchers find some evidence for quality control to bias the spread of substitution mutations in favor of those that are less harmful to mitochondrial function. Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism of mitochondrial and tissue dysfunction that occurs during aging. A thorough characterization of age-associated mtDNA somatic mutations has been hampered by the limited ability to detect low frequency mutations. Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect more than 89,000 independent somatic mtDNA mutations and show significan...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs