Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun, Chungbuk 28024, Republic of Korea.
Institutes for Translational Neuroscience (ITN) & of Human Genetics (IHG), Department of Laboratory Medicine and Pathology, University of Minnesota, Wallin Medical Bioscience Building, 2101 6th St SE, Minneapolis, MN 55455, United States.
Mitochondrion. 2019 May;46:15-21. doi: 10.1016/j.mito.2019.03.006. Epub 2019 Apr 11.
Mitochondrial genomes (mtDNA) depend on the nuclear genome with which they have evolved to provide essential replication functions and have been known to replicate as xenotransplants only in the cells of closely related species. We now report that complete mouse mitochondrial genomes can be stably transplanted into the mitochondrial network in yeast devoid of their own mtDNA. Our analyses of these xenomitochondrial yeast cells show that they are accurately replicating intact mouse mtDNA genomes without rearrangement and that these mtDNA genomes have the same overall topology as the mtDNA present in the mouse mitochondrial network (i.e., circular monomers). Moreover, non-mtDNA replication and selection sequences required for maintaining the mitochondrial genomes in bacterial hosts are dispensable in these yeast mitochondria and could be efficiently and seamlessly removed by targeted homologous recombination within the mitochondria. These findings demonstrate that the yeast mtDNA replication system is capable of accurately replicating intact mammalian mtDNA genomes without sequence loss or rearrangement and that yeast mitochondria are a highly versatile host system for engineering complete mammalian mitochondrial genomes.
线粒体基因组（mtDNA）依赖于核基因组，它们共同进化以提供必要的复制功能，并且已知只能在亲缘关系密切的物种的细胞中作为异种移植进行复制。我们现在报告说，完整的小鼠线粒体基因组可以稳定地移植到缺乏自身 mtDNA 的酵母线粒体网络中。我们对这些异种线粒体酵母细胞的分析表明，它们能够准确地复制完整的、未重排的小鼠 mtDNA 基因组，并且这些 mtDNA 基因组与存在于小鼠线粒体网络中的 mtDNA 具有相同的整体拓扑结构（即圆形单体）。此外，在细菌宿主中维持线粒体基因组所必需的非 mtDNA 复制和选择序列在这些酵母线粒体中是可有可无的，并且可以通过线粒体内部的靶向同源重组有效地、无缝地去除。这些发现表明，酵母 mtDNA 复制系统能够准确地复制完整的哺乳动物 mtDNA 基因组，而不会发生序列丢失或重排，并且酵母线粒体是工程化完整哺乳动物线粒体基因组的高度多功能宿主系统。
