Hypoxia death stimulus induces translocation of p53 protein to mitochondria: Detection by immunofluorescence on whole cells

Evidence suggests that p53 induces cell death by a dual mode of action involving activation of target genes and transcriptionally independent direct signaling. Mitochondria are major signal transducers in apoptosis. We recently discovered that a fraction of induced p53 protein rapidly translocates t...

Full description

Saved in:
Bibliographic Details
Published in:FEBS letters 2001-01, Vol.488 (3), p.110-115
Main Authors: Sansome, Christine, Zaika, Alex, Marchenko, Natalie D, Moll, Ute M
Format: Article
Language:English
Subjects:
Apoptosis
Blotting, Western
Cell Line
Cell Respiration
Deferoxamine - metabolism
Fluorescent Antibody Technique
Humans
Hypoxia
Immunofluorescence
In Situ Nick-End Labeling
Intracellular Membranes - chemistry
Intracellular Membranes - metabolism
Mitochondria - metabolism
Mitochondrial localization
Oxygen - metabolism
p53
Protein Transport
Signal Transduction
Trypsin - metabolism
Tumor Suppressor Protein p53 - deficiency
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Evidence suggests that p53 induces cell death by a dual mode of action involving activation of target genes and transcriptionally independent direct signaling. Mitochondria are major signal transducers in apoptosis. We recently discovered that a fraction of induced p53 protein rapidly translocates to mitochondria during p53-dependent apoptosis, but not during p53-independent apoptosis or p53-mediated cell cycle arrest. Importantly, specific targeting of p53 to mitochondria was sufficient to induce apoptosis in p53-deficient tumor cells. This led us to propose a model where p53 exerts a direct apoptogenic role at the mitochondria, thereby enhancing the transcription-dependent apoptosis of p53. Here we show for the first time that mitochondrial localization of endogenous p53 can be visualized by immunofluorescence of whole cells when stressed by hypoxic conditions. Suborganellar localization by limited trypsin digestion of isolated mitochondria from stressed cells suggests that a significant amount of mitochondrial p53 is located at the surface of the organelle. This mitochondrial association can be reproduced in vitro with purified p53. Together, our data provide further evidence for an apoptogenic signaling role of p53 protein in vivo at the level of the mitochondria.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(00)02368-1