title: Mitochondria harbouring mutant mtDNA--a cuckoo in the nest?
abstract: Mutations of the mitochondrial DNA (mtDNA) are associated with a number of human diseases. To become relevant in terms of pathology, a mutation must generally affect at least 50-70% of mtDNA molecules in a tissue. One way to reach this level is by inheritance. Mitotic segregation of mtDNA in the female germline can result in large increases in the percentage of mutant mtDNA between generations. A different explanation is required if a particular mtDNA mutation accumulates over time in somatic cells. We discuss the possibility that mutant mtDNA, by causing deficient oxidative phosphorylation, may become preferentially replicated and may thus thrive in the cell like a cuckoo in the nest. However, despite preferential replication, a de novo mtDNA mutation will be confined to that particular cell or a small clone of daughter cells. Significant accumulation can only occur if the cell harbouring the mutant mtDNA undergoes malignant transformation and therefore starts proliferating continuously. This type of amplification of mutant mtDNA has recently been demonstrated in certain bone marrow disorders (myelodysplastic syndromes) and in colon cancer cell lines. Finally, in postmitotic tissues, an inherited mutation which is present in virtually all cells of the tissue, may accumulate through replicative advantage. This may contribute to the development of degenerative diseases.
authors.affiliation: Institute of Biochemistry, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Hofhaus
authors.forename: N
authors.initials: N
authors.lastname: Gattermann
mesh_terms: D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial