Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling

• DOI: 10.1083/jcb.201708191
• Publication Date: 2018-02-08T16:46:45Z
• Authors: Dominic B. Bernkopf; Kowcee Jalal; Martina Brückner; Karl X. Knaup; Marc Gentzel; Alexandra Schambony; Jürgen Behrens
• Keywords: Transcriptional Activation; 0303 health sciences; Organelle Biogenesis; Transcription, Genetic; Protein Stability; Mitochondria; Mitochondrial Proteins; Mice; 03 medical and health sciences; HEK293 Cells; Axin Protein; Proteolysis; Phosphoprotein Phosphatases; Proton Ionophores; Animals; Humans; Phosphorylation; Wnt Signaling Pathway; Research Articles; beta Catenin; HeLa Cells; Protein Binding

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