Mitochondrial matrix P53 sensitizes cells to oxidative stress.

Mitochondrial matrix P53 sensitizes cells to oxidative stress.
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DOI:
10.1016/j.mito.2013.03.001
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发表时间:
2013-07
期刊:
影响因子:
4.4
通讯作者:
Lewis W
Lewis W
中科院分区:
生物学3区
文献类型:
--
作者:
Koczor CA;Torres RA;Fields EJ;Boyd A;Lewis W

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利用HepG2细胞中线粒体基质特异性P53结构(称为P53-290)来确定氧化应激后线粒体基质中P53的影响。过氧化氢暴露对p53-290和载体细胞的细胞增殖抑制作用相似,而p53-290细胞在1 mM的过氧化氢作用下表现出细胞活力下降(~85%的活性)。P5 3-290细胞线粒体DNA(MtDNA)丰度呈剂量依赖性下降,而载体细胞则无明显变化。血氧分析显示P53-290细胞的最大呼吸和储备能力降低。我们的结果表明,线粒体基质p53通过减少线粒体DNA丰度和线粒体功能而使细胞对氧化应激敏感。
A mitochondrial matrix-specific p53 construct (termed p53–290) in HepG2 cells was utilized to determine the impact of p53 in the mitochondrial matrix following oxidative stress. H2O2 exposure reduced cellular proliferation similarly in both p53–290 and vector cells, and p53–290 cells demonstrating decreased cell viability at 1 mM H2O2 (~85% viable). Mitochondrial DNA (mtDNA) abundance was decreased in a dose-dependent manner in p53–290 cells while no change was observed in vector cells. Oximetric analysis revealed reduced maximal respiration and reserve capacity in p53–290 cells. Our results demonstrate that mitochondrial matrix p53 sensitizes cells to oxidative stress by reducing mtDNA abundance and mitochondrial function.
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