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Thursday, February 15th, 2018
Table of Contents

1 Introduction
5 PMID
 [F] Diseases Research  / PubMed Research Articles  /
Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling.

PubMed

 

Resource

The Journal of cell biology Feb ; ()

Authors

Bernkopf DB1; Jalal K2; Brückner M3; Knaup KX4; Gentzel M5; Schambony A6; Behrens J7;

Author Information
  • 1Experimental Medicine II, Nikolaus Fiebiger Center, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • 2Experimental Medicine II, Nikolaus Fiebiger Center, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • 3Experimental Medicine II, Nikolaus Fiebiger Center, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • 4Department of Nephrology and Hypertension, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • 5Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
  • 6Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • 7Experimental Medicine II, Nikolaus Fiebiger Center, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany juergen.behrens@fau.de.

Abstract

Mitochondrial abundance is dynamically regulated and was previously shown to be increased by Wnt/β-catenin signaling. Pgam5 is a mitochondrial phosphatase which is cleaved by the rhomboid protease presenilin-associated rhomboid-like protein (PARL) and released from membranes after mitochondrial stress. In this study, we show that Pgam5 interacts with the Wnt pathway component axin in the cytosol, blocks axin-mediated β-catenin degradation, and increases β-catenin levels and β-catenin-dependent transcription. Pgam5 stabilized β-catenin by inducing its dephosphorylation in an axin-dependent manner. Mitochondrial stress triggered by carbonyl cyanide m-chlorophenyl hydrazone (CCCP) treatment led to cytosolic release of endogenous Pgam5 and subsequent dephosphorylation of β-catenin, which was strongly diminished in Pgam5 and PARL knockout cells. Similarly, hypoxic stress generated cytosolic Pgam5 and led to stabilization of β-catenin, which was abolished by Pgam5 knockout. Cells stably expressing cytosolic Pgam5 exhibit elevated β-catenin levels and increased mitochondrial numbers. Our study reveals a novel mechanism by which damaged mitochondria might induce replenishment of the mitochondrial pool by cell-intrinsic activation of Wnt signaling via the Pgam5-β-catenin axis.

© 2018 Bernkopf et al.

PMID

29438981

Others

Publication Type: Journal Article


This article is licensed under the the National Library of Medicine License. It uses material from the PubMed National Library of Medicine Data.


Last Modified:   2016-03-27


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