Caveolin-1 impairs PKA-DRP1-mediated remodelling of ER-mitochondria communication during the early phase of ER stress.
Caveolin-1 impairs PKA-DRP1-mediated remodelling of ER-mitochondria communication during the early phase of ER stress.
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DOI：
10.1038/s41418-018-0197-1
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发表时间：
2019-07
影响因子：
12.4
通讯作者：
Lavandero S
中科院分区：
文献类型：
--
作者：
Bravo-Sagua R;Parra V;Ortiz-Sandoval C;Navarro-Marquez M;Rodríguez AE;Diaz-Valdivia N;Sanhueza C;Lopez-Crisosto C;Tahbaz N;Rothermel BA;Hill JA;Cifuentes M;Simmen T;Quest AFG;Lavandero S
内质网和线粒体之间的密切联系使相互的钙离子交换成为线粒体生物能量学调节的关键机制。在内质网应激的早期阶段，这种细胞器间的通讯作为一种确保细胞存活的适应机制而增加。然而，支配这种反应的信号通路还没有被描述出来。在这里，我们发现小窝蛋白-1定位于内质网-线粒体界面，在那里它损害了内质网-线粒体接触的重塑，抑制了钙离子的传递，使线粒体生物能量学对内质网应激没有反应。相反，蛋白激酶A在内质网应激时促进内质网和线粒体的重塑和通讯，以促进细胞器动力学和钙离子转运，并在适应性反应中增强线粒体的生物能量学。重要的是，小窝蛋白-1的表达减少了蛋白激酶A的信号，这从GTPase Dynamin相关蛋白1的磷酸化受损和细胞器分布的改变中得到了证明，从而增加了细胞对内质网应激的死亡。总之，小窝蛋白-1阻止了应激诱导的蛋白激酶A依赖的内质网-线粒体通讯的重塑。
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.
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影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1186/s12964-014-0068-4
发表时间：
2014-11-07
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Gutiérrez T;Parra V;Troncoso R;Pennanen C;Contreras-Ferrat A;Vasquez-Trincado C;Morales PE;Lopez-Crisosto C;Sotomayor-Flores C;Chiong M;Rothermel BA;Lavandero S
通讯作者：
Lavandero S
影响因子：
4.6
作者：
Bravo-Sagua R;López-Crisosto C;Parra V;Rodriguez-Peña M;Rothermel BA;Quest AF;Lavandero S
通讯作者：
Lavandero S
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Cárdenas C;Miller RA;Smith I;Bui T;Molgó J;Müller M;Vais H;Cheung KH;Yang J;Parker I;Thompson CB;Birnbaum MJ;Hallows KR;Foskett JK
通讯作者：
Foskett JK