Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling.
J Cell Biol
; 217(4): 1383-1394, 2018 04 02.
Article
em En
| MEDLINE
| ID: mdl-29438981
ABSTRACT
Mitochondrial abundance is dynamically regulated and was previously shown to be increased by Wnt/ß-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 ß-catenin degradation, and increases ß-catenin levels and ß-catenin-dependent transcription. Pgam5 stabilized ß-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 ß-catenin, which was strongly diminished in Pgam5 and PARL knockout cells. Similarly, hypoxic stress generated cytosolic Pgam5 and led to stabilization of ß-catenin, which was abolished by Pgam5 knockout. Cells stably expressing cytosolic Pgam5 exhibit elevated ß-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-ß-catenin axis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biogênese de Organelas
/
Fosfoproteínas Fosfatases
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Proteínas Mitocondriais
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Via de Sinalização Wnt
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Mitocôndrias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha