Dear Editor,Endonuclease G (EndoG) is a conserved nuclease that, under normal conditions, is found in the intermembrane space of mitochondria and plays important roles in multiple cellular processes in diverse organisms, including mitochondrial DNA (mtDNA) replication1, apoptosis2,3, mitochondrial maintenance4, neurodegeneration5, and paternal mitochondrial elimination (PME)6.

亲爱的编辑，核酸内切酶G（EndoG）是一种保守的核酸酶，在正常条件下，存在于线粒体的膜间隙中，在多种生物体的多种细胞过程中发挥重要作用，包括线粒体DNA（mtDNA）复制1，细胞凋亡2,3，线粒体维持4，神经退行性变5和父系线粒体消除（PME）6。

Thus, identification and analysis of factors that regulate the activity of EndoG is crucial for understanding how these important cellular events are regulated.One important EndoG regulator is apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase important for apoptosis7. In C. elegans, the worm AIF homolog, WAH-1, is found to be an interacting protein and activator of the C.

因此，鉴定和分析调节EndoG活性的因素对于理解如何调节这些重要的细胞事件至关重要。一种重要的EndoG调节剂是凋亡诱导因子（AIF），一种对细胞凋亡很重要的线粒体氧化还原酶7。在秀丽隐杆线虫中，发现蠕虫AIF同源物WAH-1是C的相互作用蛋白和激活剂。

elegans EndoG homolog, CPS-63,8. Reduction or loss of wah-1 activity caused by RNA interference or wah-1 deletion results in a delay of cell death phenotype similar to that of the cps-6 mutant3,8,9. The activity of CPS-6 is also regulated by oxidation-reduction (redox) conditions9. Under reducing conditions, CPS-6 forms a dimeric complex that exhibits high nuclease activity, whereas under oxidative conditions with increased levels of reactive oxygen species, CPS-6 dimers disassociate into monomers with diminished nuclease activity9.

线虫EndoG同源物CPS-63,8。由RNA干扰或wah-1缺失引起的wah-1活性的降低或丧失导致细胞死亡表型的延迟，类似于cps-6突变体3,8,9。CPS-6的活性也受氧化还原（氧化还原）条件的调节9。在还原条件下，CPS-6形成具有高核酸酶活性的二聚体复合物，而在活性氧水平升高的氧化条件下，CPS-6二聚体解离成核酸酶活性降低的单体9。

WAH-1 appears to bind CPS-6 to stabilize the CPS-6 dimer based on in vitro assays. Like AIF, WAH-1 is located in mitochondria and relocated from mitochondria to the nucleus during apoptosis7,8, suggesting that WAH-1 and CPS-6 could interact physically in mitochondria and cooperate to affect apoptosis and other cellular processes.

基于体外测定，WAH-1似乎结合CPS-6以稳定CPS-6二聚体。像AIF一样，WAH-1位于线粒体中，并在凋亡过程中从线粒体重新定位到细胞核7,8，这表明WAH-1和CPS-6可以在线粒体中发生物理相互作用，并协同影响细胞凋亡和其他细胞过程。

In mammals, AIF also plays a role in oxidative phosphorylation and interacts with multiple proteins10. Mutations in AIF cause neurodegeneration, muscular defect.

在哺乳动物中，AIF也在氧化磷酸化中发挥作用，并与多种蛋白质相互作用10。AIF突变会导致神经变性，肌肉缺陷。

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Download referencesAcknowledgementsWe thank G.S. Ou for providing split GFP plasmids. This work was partly supported by a fellowship from US NINDS (F32NS124826 to G.R.) and a grant from US NIH (R35GM118188 to D.X.).Author informationAuthor notesThese authors contributed equally: Shanshan Li, Graham Redweik.Authors and AffiliationsSchool of Life Sciences, Tsinghua University, Beijing, ChinaShanshan LiDepartment of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, USAGraham Redweik & Ding XueInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, ChinaJason L.

下载参考文献致谢我们感谢G.S.Ou提供分裂的GFP质粒。这项工作得到了美国NINDS（F32NS124826授予G.R.）的奖学金和美国国立卫生研究院（R35GM118188授予D.X.）的资助。作者信息作者注意到这些作者做出了同样的贡献：Shanshan Li，Graham Redweik。作者和附属机构清华大学生命科学学院，北京，科罗拉多大学分子，细胞和发育生物学系，科罗拉多大学博尔德分校，USAGraham Redweik＆Ding XUE中国台湾台北中央研究院分子生物学研究所Jason L。

J. Lin, Yi-Ning Chen & Hanna S. YuanAuthorsShanshan LiView author publicationsYou can also search for this author in.

J、 Lin，Yining Chen和Hanna S.Yuan作者Shanshan LiView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsS.L. generated the split GFP knockin strains and performed related analyses. G.R. performed neurodegeneration assays. J.L., Y.C. and H.Y. constructed the structural model and performed in vitro binding assays. D.X. conceived and supervised the project.

PubMed谷歌学术贡献。五十、 产生分裂的GFP敲入菌株并进行相关分析。G、 R.进行神经变性测定。J、 L.，Y.C.和H.Y.构建了结构模型并进行了体外结合测定。D、 。

S.L., G.R., H.Y. and D.X. analyzed data and wrote the manuscript.Corresponding authorCorrespondence to.

S、 。对应作者对应。

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Reprints and permissionsAbout this articleCite this articleLi, S., Redweik, G., Lin, J.L.J. et al. Probing the importance of AIF interaction with endonuclease G in mitochondrial inheritance and neurodegeneration.

转载和许可本文引用本文Li，S.，Redweik，G.，Lin，J.L.J.等人探讨AIF与核酸内切酶G相互作用在线粒体遗传和神经变性中的重要性。

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