Temperature-Dependent Formation of Dimers and Oligomers of Mitochondrial DNA in Cells Transformed by a Thermosensitive Mutant of Rous Sarcoma Virus

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In chick-embryo fibroblasts infected by T5, a temperature-sensitive mutant of Schmidt-Ruppin Rous sarcoma virus, the level of catenated dimeric and oligomeric mitochondrial DNA is temperature-dependent and correlates with the phenotypic manifestation of transformation. At the permissive temperature (36°), where transformation is expressed, the 2- to 3-fold elevated level characteristic of cells transformed by the wild-type Rous sarcoma virus was observed, but at the nonpermissive temperature (41°), at which cells appear normal and behave normally, the oligomer level was characteristic of uninfected cells. Temperature shifts from 41 to 36° and vice versa resulted in phenotypic reversion and reversals of the respective levels of multiple-length DNA. Cellular growth rates were not altered. Treatment of control cells with cycloheximide resulted in a 5-fold increase of oligomeric DNA, whereas exposure to 9-β-D-arabinofuranosyladenine had little effect. With both inhibitors, nuclear but not mitochondrial DNA synthesis was inhibited. The possible relation of formation of oligomeric mitochondrial DNA to alterations in the mitochondrial membranes of transformed cells and to inhibition of protein synthesis in the cytoplasm is discussed.

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