title: Mitochondrial DNA mutations in ageing and disease: implications for HIV?
abstract: Mitochondrial DNA (mtDNA) mutations cause neurological and multisystem disease. Somatic (acquired) mtDNA mutations are also associated with degenerative diseases and with normal human ageing. It is well established that certain nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral drugs cause inhibition of the mtDNA polymerase, pol γ, leading to a reduction in mtDNA content (depletion). Given this effect of NRTI therapy on mtDNA replication, it is plausible that NRTI treatment may also lead to increased mtDNA mutations. Here we review recent evidence for an effect of HIV infection or NRTI therapy on mtDNA mutations, as well as discussing the methodological challenges in addressing this question. Finally, we discuss the possible implications for HIV-infected persons, with particular reference to ageing.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK. Brendan.Payne@ncl.ac.uk.
authors.forename: Brendan A I
authors.initials: BA
authors.lastname: Payne
authors.forename: Kristian
authors.initials: K
authors.lastname: Gardner
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004252:DNA Mutational Analysis / Q000295:instrumentation / Q000379:methods; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D006678:HIV / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D018894:Reverse Transcriptase Inhibitors; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human