Release of targeted p53 from the mitochondrion as an early signal during mitochondrial dysfunction

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• 作者：M.L. Green ; M.M. Pisano ; R.A. Prough ; T.B. Knudsen
• 关键词：p53 ; Mitochondria ; Rotenone ; Embryo ; PK11195 ; TspO
• 刊名：Cellular Signalling
• 出版年：2013
• 出版时间：December, 2013
• 年：2013
• 卷：25
• 期：12
• 页码：2383-2390
• 全文大小：1201 K

文摘

Increased accumulation of p53 tumor suppressor protein is an early response to low-level stressors. To investigate the fate of mitochondrial-sequestered p53, mouse embryonic fibroblast cells (MEFs) on a p53-deficient genetic background were transfected with p53-EGFP fusion protein led by a sense (m53-EGFP) or antisense (c53-EGFP) mitochondrial import signal. Rotenone exposure (100 nM, 1 h) triggered the translocation of m53-EGFP from the mitochondrion to the nucleus, thus shifting the transfected cells from a mitochondrial p53 to a nuclear p53 state. Antibodies for p53 serine phosphorylation or lysine acetylation indicated a different post-translational status of recombinant p53 in the nucleus and mitochondrion, respectively. These data suggest that cycling of p53 through the mitochondria may establish a direct pathway for p53 signaling from the mitochondria to the nucleus during mitochondrial dysfunction. PK11195, a pharmacological ligand of mitochondrial TSPO (formerly known as the peripheral-type benzodiazepine receptor), partially suppressed the release of mitochondria-sequestered p53. These findings support the notion that p53 function mediates a direct signaling pathway from the mitochondria to nucleus during mitochondrial dysfunction.