Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome.
Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome.
复制标题
DOI：
10.1371/journal.pone.0140409
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Singh KK
中科院分区：
文献类型：
--
作者：
Singh B;Li X;Owens KM;Vanniarajan A;Liang P;Singh KK
迄今为止，线粒体DNA聚合酶γ (POLG)是唯一已知存在于哺乳动物线粒体中的聚合酶。线粒体领域的一个教条是，哺乳动物细胞的线粒体中不存在其他聚合酶。在这里，我们证明了REV3 DNA聚合酶在哺乳动物线粒体中的定位。我们证明了REV3在哺乳动物组织和细胞系的线粒体中的定位。REV3与POLG和线粒体DNA结合，保护线粒体基因组免受DNA损伤。Rev3的失活导致线粒体膜电位降低，OXPHOS活性降低，葡萄糖消耗增加。相反，抑制OXPHOS会增加Rev3的表达。Rev3在人原发性乳腺肿瘤和乳腺癌细胞系中表达增加。Rev3的失活减少了细胞的迁移和侵袭，Rev3在线粒体中的定位增加了癌细胞的存活和侵袭潜力。综上所述，我们证明REV3在哺乳动物线粒体中起作用，线粒体REV3与细胞的致瘤潜能有关。
To date, mitochondrial DNA polymerase γ (POLG) is the only polymerase known to be present in mammalian mitochondria. A dogma in the mitochondria field is that there is no other polymerase present in the mitochondria of mammalian cells. Here we demonstrate localization of REV3 DNA polymerase in the mammalian mitochondria. We demonstrate localization of REV3 in the mitochondria of mammalian tissue as well as cell lines. REV3 associates with POLG and mitochondrial DNA and protects the mitochondrial genome from DNA damage. Inactivation of Rev3 leads to reduced mitochondrial membrane potential, reduced OXPHOS activity, and increased glucose consumption. Conversely, inhibition of the OXPHOS increases expression of Rev3. Rev3 expression is increased in human primary breast tumors and breast cancer cell lines. Inactivation of Rev3 decreases cell migration and invasion, and localization of Rev3 in mitochondria increases survival and the invasive potential of cancer cells. Taken together, we demonstrate that REV3 functions in mammalian mitochondria and that mitochondrial REV3 is associated with the tumorigenic potential of cells.