The consequences of reprogramming a somatic cell for mitochondrial DNA transmission, inheritance and replication

Reprogramming promotes the generation of animals and pluripotent stem cells from a variety of somatic cells, which was not previously possible through natural or in vitro fertilisation. Whilst much of the debate on reprogramming has been related to epigenetic regulation, chromosomal gene expression and the establishment of pluripotency, the regulation and expression of the genes encoded by the mitochondrial genome have been largely ignored. The maternally inherited mitochondrial genome encodes 13 key proteins of the electron transfer chain, which is the cell's major generator of ATP through the biochemical process of oxidative phosphorylation (OXPHOS). OXPHOS is essential for driving a large number of cellular functions. Mitochondrial DNA (mtDNA) rearrangements and depletion can lead to phenotypes that are either severely debilitating or lethal. Following natural fertilisation, mtDNA is maternally inherited and its copy number is strictly regulated during early development and differentiation. This ensures that specialised cells acquire the appropriate numbers of mtDNA to meet their specific requirements for OXPHOS-generated ATP. We discuss how somatic cell nuclear transfer disrupts the strict control of mtDNA replication and how this will affect cellular function in specialised cells. We discuss how the transfer of the somatic cell results in the loss of maternal-only inheritance of mtDNA and the consequences of this. We further highlight the importance of choosing the appropriate recipient oocyte, as the electron transfer chain is highly dependent on chromosomall-nd mtDNA-encoded genes and their compatibility is essential to cellular and offspring function and survival.