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

Jie Zhuang, Ping Yuan Wang, Xinglu Huang, Xiaoyuan Chen, Ju Gyeong Kang, Paul M. Hwang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)17356-17361
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number43
DOIs
StatePublished - Oct 22 2013

Keywords

  • DNA repair
  • Mitochondrial DNA
  • Mutant p53

ASJC Scopus subject areas

  • General

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