Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling

Bernkopf D, Jalal K, Brückner M, Knaup K, Gentzel M, Schambony A, Behrens J (2018)

Publication Type: Journal article

Publication year: 2018

Journal

The Journal of Cell Biology Rockefeller University Press

Book Volume: 217

Pages Range: 1383-1394

Journal Issue: 4

DOI: 10.1083/jcb.201708191

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.

Authors with CRIS profile

Dominic Bernkopf Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung) Kowcee Jalal Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung) Martina Brückner Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung) Karl Knaup Department of Medicine 4 – Nephrology and Hypertension Alexandra Schambony Lehrstuhl für Entwicklungsbiologie Jürgen Behrens Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung)

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Max-Planck-Institut für molekulare Zellbiologie und Genetik / Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) DE Germany (DE)

How to cite

APA:

Bernkopf, D., Jalal, K., Brückner, M., Knaup, K., Gentzel, M., Schambony, A., & Behrens, J. (2018). Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling. The Journal of Cell Biology, 217(4), 1383-1394. https://dx.doi.org/10.1083/jcb.201708191

MLA:

Bernkopf, Dominic, et al. "Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling." The Journal of Cell Biology 217.4 (2018): 1383-1394.

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