Caveolin-1 impairs PKA-DRP1-mediated remodelling of ER–mitochondria communication during the early phase of ER stress

Roberto Bravo-Sagua, Valentina Parra, Carolina Ortiz-Sandoval, Mario Navarro-Marquez, Andrea E. Rodríguez, Natalia Diaz-Valdivia, Carlos Sanhueza, Camila Lopez-Crisosto, Nasser Tahbaz, Beverly A Rothermel, Joseph A Hill, Mariana Cifuentes, Thomas Simmen, Andrew F.G. Quest, Sergio Lavandero

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Close contacts between endoplasmic reticulum and mitochondria enable reciprocal Ca2+ exchange, a key mechanism in the regulation of mitochondrial bioenergetics. During the early phase of endoplasmic reticulum stress, this inter-organellar communication increases as an adaptive mechanism to ensure cell survival. The signalling pathways governing this response, however, have not been characterized. Here we show that caveolin-1 localizes to the endoplasmic reticulum–mitochondria interface, where it impairs the remodelling of endoplasmic reticulum–mitochondria contacts, quenching Ca2+ transfer and rendering mitochondrial bioenergetics unresponsive to endoplasmic reticulum stress. Protein kinase A, in contrast, promotes endoplasmic reticulum and mitochondria remodelling and communication during endoplasmic reticulum stress to promote organelle dynamics and Ca2+ transfer as well as enhance mitochondrial bioenergetics during the adaptive response. Importantly, caveolin-1 expression reduces protein kinase A signalling, as evidenced by impaired phosphorylation and alterations in organelle distribution of the GTPase dynamin-related protein 1, thereby enhancing cell death in response to endoplasmic reticulum stress. In conclusion, caveolin-1 precludes stress-induced protein kinase A-dependent remodelling of endoplasmic reticulum–mitochondria communication.

Original languageEnglish (US)
JournalCell Death and Differentiation
DOIs
Publication statusAccepted/In press - Jan 1 2018

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Bravo-Sagua, R., Parra, V., Ortiz-Sandoval, C., Navarro-Marquez, M., Rodríguez, A. E., Diaz-Valdivia, N., ... Lavandero, S. (Accepted/In press). Caveolin-1 impairs PKA-DRP1-mediated remodelling of ER–mitochondria communication during the early phase of ER stress. Cell Death and Differentiation. https://doi.org/10.1038/s41418-018-0197-1