Ribonucleotide reductase subunit p53R2 regulates mitochondria homeostasis and function in KB and PC-3 cancer cells

Xiaochen Wang, Xiyong Liu, Lijun Xue, Keqiang Zhang, Mei Ling Kuo, Shuya Hu, Bingsen Zhou, David Ann, Suzhan Zhang, Yun Yen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Ribonucleotide reductase (RR) is a rate-limiting enzyme that catalyzes de novo conversion of ribonucleotide 5′-diphosphates to the corresponding 2′-deoxynucleotide, essential for DNA synthesis and replication. The mutations or knockout of RR small subunit, p53R2, results in the depletion of mitochondrial DNA (mtDNA) in human, implying that p53R2 might play a critical role for maintaining mitochondrial homeostasis. In this study, siRNA against p53R2 knockdown approach is utilized to examine the impact of p53R2 depletion on mitochondria and to derive underlying mechanism in KB and PC-3 cancer cells. Our results reveal that the p53R2 expression not only positively correlates with mtDNA content, but also partakes in the proper mitochondria function, such as ATP synthesis, cytochrome c oxidase activity and membrane potential maintenance. Furthermore, overexpression of p53R2 reduces intracellular ROS and protects the mitochondrial membrane potential against oxidative stress. Unexpectedly, knockdown of p53R2 has a modest, if any, effect on mitochondrial and total cellular dNTP pools. Taken together, our study provides functional evidence that mitochondria is one of p53R2-targeted organelles and suggests an unexpected function of p53R2, which is beyond known RR function on dNTP synthesis, in mitochondrial homeostatic control.

Original languageEnglish
Pages (from-to)102-107
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume410
Issue number1
DOIs
Publication statusPublished - Jun 24 2011
Externally publishedYes

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Keywords

  • ATP synthesis
  • Cytochrome c oxidase
  • Membrane potential
  • Mitochondrial DNA (mtDNA) synthesis
  • P53R2 (RRM2B)

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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