TY - JOUR
T1 - Caveolin-1 impairs PKA-DRP1-mediated remodelling of ER–mitochondria communication during the early phase of ER stress
AU - Bravo-Sagua, Roberto
AU - Parra, Valentina
AU - Ortiz-Sandoval, Carolina
AU - Navarro-Marquez, Mario
AU - Rodríguez, Andrea E.
AU - Diaz-Valdivia, Natalia
AU - Sanhueza, Carlos
AU - Lopez-Crisosto, Camila
AU - Tahbaz, Nasser
AU - Rothermel, Beverly A
AU - Hill, Joseph A
AU - Cifuentes, Mariana
AU - Simmen, Thomas
AU - Quest, Andrew F.G.
AU - Lavandero, Sergio
N1 - Publisher Copyright:
© 2018, ADMC Associazione Differenziamento e Morte Cellulare.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85053417531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053417531&partnerID=8YFLogxK
U2 - 10.1038/s41418-018-0197-1
DO - 10.1038/s41418-018-0197-1
M3 - Article
C2 - 30209302
AN - SCOPUS:85053417531
SN - 1350-9047
VL - 26
SP - 1195
EP - 1212
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 7
ER -