Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondria! DNA-deficient cancer cells
Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondria! DNA-deficient cancer cells
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DOI：
10.7554/elife.22187
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发表时间：
2017-02-15
期刊：
影响因子：
7.7
通讯作者：
Neuzil, Jiri
中科院分区：
文献类型：
--
作者：
Dong, Lan-Feng;Kovarova, Jaromira;Neuzil, Jiri
最近，我们发现，在同源小鼠中，缺乏线粒体（mt）DNA的细胞（rho（0）细胞）产生的肿瘤与宿主mtDNA的获得有关。然而，mtDNA在细胞间运动的机制仍然没有得到解决。为了确定mtDNA的转移是否涉及整个线粒体，我们将B16 rho（0）小鼠黑色素瘤细胞注射到在线粒体中表达红色荧光蛋白的同基因C576116N（su9DsRed2）小鼠中。我们的文件，线粒体DNA是通过从宿主动物的整个线粒体转移，导致线粒体呼吸正常化。此外，在B16 rho（0）细胞中，通过shRNA敲低关键的线粒体复合物I（NDUFV 1）和复合物II（SDHC）亚基，消除或显著延迟了它们形成肿瘤的能力。总的来说，这些结果表明，完整的线粒体及其mtDNA有效载荷在发展中的肿瘤中转移，并为氧化磷酸化在癌症中的重要作用提供了功能证据。
Recently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (rho(0) cells) is linked to the acquisition of the host mtDNA. However, the mechanism of mtDNA movement between cells remains unresolved. To determine whether the transfer of mtDNA involves whole mitochondria, we injected B16 rho(0) mouse melanoma cells into syngeneic C576116N(su9DsRed2) mice that express red fluorescent protein in their mitochondria. We document that mtDNA is acquired by transfer of whole mitochondria from the host animal, leading to normalisation of mitochondrial respiration. Additionally, knockdown of key mitochondrial complex I (NDUFV1) and complex II (SDHC) subunits by shRNA in B16 rho(0) cells abolished or significantly retarded their ability to form tumours. Collectively, these results show that intact mitochondria with their mtDNA payload are transferred in the developing tumour, and provide functional evidence for an essential role of oxidative phosphorylation in cancer.