Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling

Research output: Contribution to journalResearch articleContributedpeer-review


  • Dominic B. Bernkopf - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Kowcee Jalal - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Martina Brückner - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Karl X. Knaup - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Marc Gentzel - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Alexandra Schambony - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Jürgen Behrens - , Friedrich-Alexander University Erlangen-Nürnberg (Author)


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.


Original languageEnglish
Pages (from-to)1383-1394
Number of pages12
JournalJournal of Cell Biology
Issue number4
Publication statusPublished - 1 Apr 2018
Externally publishedYes

External IDs

PubMed 29438981
ORCID /0000-0002-4482-6010/work/142251025


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