title: Mitochondrial DNA copy number and replication in reprogramming and differentiation.
abstract: Until recently, it was thought that the role of the mitochondrial genome was confined to encoding key proteins that generate ATP through the process of oxidative phosphorylation in the electron transfer chain. However, with increasing new evidence, it is apparent that the mitochondrial genome has a major role to play in a number of diseases and phenotypes. For example, mitochondrial variants and copy number have been implicated in the processes of fertilisation outcome and development and the onset of tumorigenesis. On the other hand, mitochondrial DNA (mtDNA) haplotypes have been implicated in a variety of diseases and most likely account for the adaptation that our ancestors achieved in order that they were fit for their environments. The mechanisms, which enable the mitochondrial genome to either protect or promote the disease phenotype, require further elucidation. However, there appears to be significant 'crosstalk' between the chromosomal and mitochondrial genomes that enable this to take place. One such mechanism is the regulation of DNA methylation by mitochondrial DNA, which is often perturbed in reprogrammed cells that have undergone dedifferentiation and affects mitochondrial DNA copy number. Furthermore, it appears that the mitochondrial genome interacts with the chromosomal genome to regulate the transcription of key genes at certain stages during development. Additionally, the mitochondrial genome can accumulate a series of mtDNA variants, which can lead to diseases such as cancer. It is likely that a combination of certain mitochondrial variants and aberrant patterns of mtDNA copy number could indeed account for many diseases that have previously been unaccounted for. This review focuses on the role that the mitochondrial genome plays especially during early stages of development and in cancer.
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, and the ​Department of Molecular and Translational Science, Monash University, 27-31 Wright Street, Clayton, VIC 3168, Australia. Electronic address: justin.stjohn@hudson.org.au.
authors.forename: Justin C
authors.initials: JC
authors.lastname: St John
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D004272:DNA, Mitochondrial
keywords: Differentiation; Mitochondrial DNA; Pluripotency; Reprogramming; Stem cells; Tumour