Mitochondrial DNA dynamics

Mutations in mitochondrial DNA (mtDNA) cause several neuromuscular disorders. Frequently these mutations are heteroplasmic – i.e. mutant and wild-type molecules coexist within the same cell. It is therefore important to define the mechanisms that govern the organization, mobility and segregation of mtDNA in human cells. Using antibodies directed against DNA, mtDNA-binding proteins and other mitochondrial proteins, Manuel Rojo and co-workers have analysed the localization and dynamics of mtDNA in cultured human cells (see p. 2653). They observe that the cell's mitochondrial network possesses several hundred nucleoids, each of which contains 2-8 mtDNA molecules along with associated proteins. They then show that these exhibit a mobility similar to that of soluble mitochondrial matrix proteins and can spread efficiently into mitochondria lacking mtDNA following cell fusion. By contrast, such fusion-mediated transfer is more limited if the recipient mitochondria already contain mtDNA. This reduced mobility leads to spatial segregation of different mtDNA molecules and has significant implications for individuals who have a mixture of mutant and wild-type mtDNA molecules.