title: Unexpected nonrandom mitochondrial DNA segregation in human cell hybrids.
abstract: Cells from patients with various inherited mitochondrial myopathies have been reported to contain more than one type of mitochondrial DNA (heteroplasmy). It has been suggested that the degree of heteroplasmy may be important in the clinical manifestations of these diseases; however, little is known about the origin or inheritance of organellar heteroplasmy in mammalian cells. In order to gain an understanding of mechanisms of genetic transmission of mitochondrial DNA, we have made somatic cell hybrids by fusion of cells containing mitochondrial DNA with differences in their restriction endonuclease patterns. This permits the artificial mixing of mitochondria and the study of mitochondrial DNA segregation patterns. In this report evidence will be presented to show that there are differences in the propagational abilities of mitochondrial genomes in many intraspecies human cell hybrids crosses. This was unexpected since it is generally believed that mitochondrial DNA is under relaxed cellular controls and that random transmission of mitochondrial DNA to daughter cells occurs at mitosis. Mitochondrial DNA from tumorigenic HeLa cells, which is initially present in somatic cell hybrids made by fusion of HeLa cells to nontumorigenic cells, is usually lost after several weeks of continuous cell culture. However, when HeLa cells are fused to other tumorigenic cells, random mitochondrial DNA segregation occurs. Thus the tumorigenicity (perhaps state of differentiation) of the parental cells used in these fusions often correlates with the type of mitochondrial DNA retained.
authors.affiliation: University of Texas Southwestern Medical Center, Department of Cell Biology, Dallas 75235.
authors.forename: J W
authors.initials: JW
authors.lastname: Shay
authors.forename: S
authors.initials: S
authors.lastname: Ishii
mesh_terms: D004273:DNA, Neoplasm / Q000032:analysis*; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells / Q000648:ultrastructure*; D008928:Mitochondria; D008938:Mitosis; D013489:Suppression, Genetic
chemical_list: D004273:DNA, Neoplasm