Home » Key Scientific Articles » Release of targeted p53 from the mitochondrion as an early signal during mitochondrial dysfunction.

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

Green ML, Pisano MM, Prough RA, Knudsen TB.

Cell Signal. 2013;25(12):2383-90.

Department of Molecular, Cellular and Craniofacial Biology, University of Louisville, 501 S. Preston St., Louisville, KY 40202, USA; Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA. Electronic address: [email protected]

 

 

Abstract

 

Increased accumulation of p53 tumor suppressor protein is an early response to low-level stressors. To investigate the fate ofmitochondrial-sequestered p53, mouse embryonic fibroblast cells (MEFs) on a p53-deficient genetic background were transfected withp53-EGFP fusion protein led by a sense (m53-EGFP) or antisense (c53-EGFP) mitochondrial import signal. Rotenone exposure (100nM, 1h) triggered the translocation of m53-EGFP from the mitochondrion to the nucleus, thus shifting the transfected cells from amitochondrial 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.

© 2013. Published by Elsevier Inc. All rights reserved.

Go To PubMed