Mitochondrial disulfide relay mediates translocation of p53 and partitions its subcellular activity

Zhuang J.; Wang P.-Y.; Huang X.Chen X.Kang J.-G.Hwang P.M.

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Mitochondrial disulfide relay mediates translocation of p53 and partitions its subcellular activity

机译：Mitochondrial disulfide relay mediates translocation of p53 and partitions its subcellular activity

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P53, a critical tumor suppressor, regulates mitochondrial respiration, but how a nuclear protein can orchestrate the function of an organelle encoded by two separate genomes, both of which require p53 for their integrity, remains unclear. Here we report that the mammalian homolog of the yeast mitochondrial disulfide relay protein Mia40 (CHCHD4) is necessary for the respiratorydependent translocation of p53 into the mitochondria. In the setting of oxidative stress, increased CHCHD4 expression partitions p53 into the mitochondria and protects its genomic integrity while decreasing p53 nuclear localization and transcriptional activity. Conversely, decreased CHCHD4 expression prevents the mitochondrial translocation of p53 while augmenting its nuclear localization and activity. Thus, the mitochondrial disulfide relay system allows p53 to regulate two spatially segregated genomes depending on oxidative metabolic activity.

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来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第43期|17356-17361|共6页
作者
Zhuang J.; Wang P.-Y.; Huang X.Chen X.Kang J.-G.Hwang P.M.;
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作者单位

Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States;

Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
DNA repair; Mitochondrial DNA; Mutant p53;

Mitochondrial disulfide relay mediates translocation of p53 and partitions its subcellular activity

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