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Property "Has-20abstract" (as page type) with input value "-5B-5BImage:MITOEAGLE-2Dlogo.jpg-7Cleft-7C100px-7Clink=http:-2F-2Fwww.mitoeagle.org-2Findex.php-2FMitoEAGLE-7CCOST-20Action-20MitoEAGLE-5D-5D-0AContact-20points-20between-20the-20endoplasmic-20reticulum-20(ER)-20and-20mitochondria-20enable-20Ca-3Csup-3E2+-3C-2Fsup-3E-20transfer-20between-20both-20organelles,-20which-20is-20a-20key-20mechanism-20in-20the-20modulation-20of-20mitochondrial-20metabolism.-20During-20early-20ER-20stress,-20this-20communication-20increases-20as-20an-20adaptive-20mechanism-20-5B1-5D.-20The-20signalling-20pathways-20controlling-20this-20response,-20however,-20are-20yet-20to-20be-20fully-20characterized.-20As-20candidates,-20we-20hypothesised-20that-20Caveolin-2D1-20(CAV1)-20may-20be-20implicated,-20as-20it-20is-20enriched-20at-20ERā€“mitochondria-20contact-20sites-20-5B2-5D.-20PKA-20was-20also-20a-20candidate,-20as-20its-20activity-20has-20been-20shown-20to-20regulate-20organelle-20dynamics-20-5B3-5D.-20-0A-0AWe-20used-20wild-20type-20HeLa-20cells-20for-20overexpressing-20CAV1.-20Early-20ER-20stress-20was-20induced-20with-20tunicamycin-200,5-20Āµg-2FmL-20for-204-20h.-20We-20measured-20ERā€“mitochondria-20contacts-20via-20electron-20microscopy-20and-20confocal-20microscopy.-20For-20Ca-3Csup-3E2+-3C-2Fsup-3E-20transfer,-20we-20used-20the-20fluorescent-20probe-20Rhod-2DFF.-20To-20evaluate-20mitochondrial-20respiration,-20we-20measured-20a-20Clarkā€™s-20electrode.-20DRP1-20phosphorylation-20was-20analysed-20through-20western-20blot.-20Cell-20viability-20was-20determined-20though-20annexin-20V-20staining-20using-20flow-20cytometry.-0A-0AEarly-20ER-20stress-20augmented-20ERā€“mitochondria-20contacts,-20which-20was-20prevented-20by-20CAV1-20overexpression.-20This-20rendered-20ER-2Dto-2Dmitochondria-20Ca-3Csup-3E2+-3C-2Fsup-3E-20transfer-20and-20mitochondrial-20bioenergetics-20unresponsive-20to-20ER-20stress.-20PKA-20inhibition-20with-20H89-20or-20siRNA-20also-20impaired-20the-20increase-20in-20organelle-20contacts,-20Ca-3Csup-3E2+-3C-2Fsup-3E-20transfer-20and-20mitochondrial-20respiration.-20CAV1-20overexpression-20reduced-20PKA-2Dmediated-20DRP1-20phosphorylation,-20thereby-20enhancing-20ER-20stress-2Dinduced-20cell-20death.-20Increasing-20ER-2Dmitochondria-20contacts-20with-20a-20synthetic-20linker-20restored-20cell-20survival.-0A-0AThus,-20PKA-20promotes-20the-20increase-20of-20ERā€“mitochondria-20contacts-20that-20occurs-20during-20ER-20stress.-20CAV1,-20in-20turn,-20prevents-20PKA-2Dmediated-20phosphorylation,-20also-20impairing-20said-20remodelling.-20Increasing-20ERā€“mitochondria-20contacts-20is-20necessary-20for-20the-20increase-20in-20mitochondrial-20bioenergetics-20and-20cell-20adaptation-20to-20ER-20stress-20-5B4-5D." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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