Bertrand H, Griffiths A J, Court D A, Cheng C K
Cell. 1986 Dec 5;47(5):829-37. doi: 10.1016/0092-8674(86)90525-8.
In the kalilo strains of N. intermedia, senescence is initiated by insertion of a 9.0 kb foreign nucleotide sequence, kalDNA, into mitochondrial DNA. A 9.0 kb linear DNA plasmid that is structurally homologous to the mitochondrial kalDNA insertion sequences exists in high copy numbers in close association with the nuclei of presenescent and senescent kalilo cells, but is not present in cells of long-lived normal strains. The free kalilo plasmid has not been detected in mitochondria, suggesting that the element does not contain a mitochondrial origin of replication. Unexpectedly, the nuclear plasmid, like the mitochondrial insertion element, follows a strict pattern of maternal inheritance. We surmise that the extramitochondrial plasmid is the etiological precursor of the kalDNA insertion sequences that appear in the mtDNAs of senescent cell lines and conclude that the kalilo element induces senescence because it is a mutator of mitochondrial genes.
在中间型新小绥螨的卡里洛品系中,衰老由一段9.0 kb的外源核苷酸序列kalDNA插入线粒体DNA引发。一种9.0 kb的线性DNA质粒,其结构与线粒体kalDNA插入序列同源,以高拷贝数存在于衰老前和衰老的卡里洛细胞的细胞核附近,但在长寿正常品系的细胞中不存在。在线粒体中未检测到游离的卡里洛质粒,这表明该元件不包含线粒体复制起点。出乎意料的是,核质粒与线粒体插入元件一样,遵循严格的母系遗传模式。我们推测线粒体外质粒是衰老细胞系线粒体DNA中出现的kalDNA插入序列的病因前体,并得出结论,卡里洛元件诱导衰老,因为它是线粒体基因的诱变剂。