Human mitochondrial DNA replication machinery and disease

The human mitochondrial genome is replicated by DNA polymerase γ in concert with key components of the mitochondrial DNA (mtDNA) replication machinery. Defects in mtDNA replication or nucleotide metabolism cause deletions, point mutations, or depletion of mtDNA. The resulting loss of cellular respiration ultimately induces mitochondrial genetic diseases, including mtDNA depletion syndromes (MDS) such as Alpers or early infantile hepatocerebral syndromes, and mtDNA deletion disorders such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. Here we review the current literature regarding human mtDNA replication and heritable disorders caused by genetic changes of the POLG, POLG2, Twinkle, RNASEH1, DNA2, and MGME1 genes.Current Opinion in Genetics & Development 2016, 38:52-62This review comes from a themed issue on Molecular and genetic bases of diseaseEdited by Jason Bielas and Carolyn SuzukiFor a complete overview see the Issue and the EditorialAvailable online 9th April 2016http://dx.doi.org/10.1016/j.gde.2016.03.0050959-437X/Published by Elsevier Ltd.