期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
卷 1787, 期 5, 页码 328-334出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbabio.2009.01.004
关键词
p53; mtDNA depletion; Reactive oxygen species; Mitochondrial transcription factor A; p53R2; Cancer
资金
- NIGMS NIH HHS [T32GM007223, T32 GM007223] Funding Source: Medline
- NINDS NIH HHS [R01 NS056206, R01 NS056206-02, NS056206] Funding Source: Medline
In addition to its central role in cellular stress signaling, the tumor suppressor p53 modulates mitochondrial respiration through its nuclear transcription factor activity and localizes to mitochondria, where it enhances apoptosis and suppresses mitochondrial DNA (mtDNA) mutagenesis. Here we demonstrate a new conserved role for p53 in mtDNA copy number maintenance and mitochondrial reactive oxygen species (ROS) homeostasis. In mammals, mtDNA is present at thousands of copies per cell and is essential for normal development and cell function. We show that p53 null mouse and p53 knockdown human primary fibroblasts exhibit mtDNA depletion and decreased mitochondrial mass under normal culture growth conditions. This is accompanied by a reduction of the p53R2 subunit of ribonucleotide reductase mRNA and protein and of mitochondrial transcription factor A (mtTFA) at the protein level only. Finally, p53-depleted cells exhibit significant disruption of cellular ROS homeostasis, characterized by reduced mitochondrial and cellular superoxide levels and increased cellular hydrogen peroxide. Altogether, these results elucidate additional mitochondria-related functions for p53 and implicate mtDNA depletion and ROS alterations as potentially relevant to cellular transformation, cancer cell phenotypes, and the Warburg Effect. (C) 2009 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据