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

Christine Sansome, Alexander Zaika, Natalie D. Marchenko, Ute M. Moll

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)110-115
Number of pages6
JournalFEBS Letters
Volume488
Issue number3
DOIs
StatePublished - Jan 19 2001
Externally publishedYes

Fingerprint

Mitochondria
Protein Transport
Fluorescent Antibody Technique
Apoptosis
Proteins
Cells
Cell death
Transcription
Cell Cycle Checkpoints
Transducers
Organelles
Trypsin
Transcriptional Activation
Hypoxia
Tumors
Digestion
Cell Death
Genes
Chemical activation
Association reactions

Keywords

  • Apoptosis
  • Hypoxia
  • Immunofluorescence
  • Mitochondrial localization
  • p53

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Hypoxia death stimulus induces translocation of p53 protein to mitochondria - Detection by immunofluorescence on whole cells. / Sansome, Christine; Zaika, Alexander; Marchenko, Natalie D.; Moll, Ute M.

In: FEBS Letters, Vol. 488, No. 3, 19.01.2001, p. 110-115.

Research output: Contribution to journalArticle

Sansome, Christine ; Zaika, Alexander ; Marchenko, Natalie D. ; Moll, Ute M. / Hypoxia death stimulus induces translocation of p53 protein to mitochondria - Detection by immunofluorescence on whole cells. In: FEBS Letters. 2001 ; Vol. 488, No. 3. pp. 110-115.
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