Figure 2.

Mitochondrial dynamics and its role in mtDNA distribution. (a) Schematic overview of mitochondrial fission. Constriction of the mitochondrion occurs by the endoplasmic reticulum (ER) and dynamin related protein 1 (DRP1). The final scission step is performed by DRP1 to produce multiple independent mitochondria. (b) Mitochondrial fusion outline. The mitofusins (MFNs) are responsible for tethering neighbouring mitochondria and fusing the outer membranes together. Fusion of the inner mitochondrial membrane is mediated by optic atrophy 1 (OPA1). (c) Summary of mtDNA segregation and distribution. First, newly replicated mtDNA molecules that are joined by a hemicatenane must be physically separated by topoisomerase 3α. Failure of this process results in the formation of multiple physically joined mtDNA genomes, termed mtDNA catenanes. Following separation, mitochondrial fission is required to distribute the replicated nucleoids into separate mitochondria and facilitate distribution of the genomes around the mitochondrial network. An impairment of fission results in a clustered phenotype whereby many replicated nucleoids are observed in close proximity to each other but are not physically linked together. (d) A lack of mitochondrial fusion is associated with mtDNA instability as observed by the progressive onset of mtDNA deletions and point mutations. In addition, the lack of fusion leads to a depletion in mtDNA copy number.