ArticleeLife2017
PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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Who cites it
51 citing papers in PubMed, 103 citations in OpenAlex.
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- Cellular cAMP Content and Mitochondrial Profile Define Different Subtypes of Ovarian Cancer Cells.International journal of molecular sciences · 2025Article
- Molecular regulation of mitophagy signaling in tumor microenvironment and its targeting for cancer therapy.Cytokine & growth factor reviews · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Review
- Cardiac Gene Therapy With Phosphodiesterase 2A Limits Remodeling and Arrhythmias in Mouse Models of Heart Failure.Journal of the American Heart Association · 2025Article
- Cardiac cGMP Regulation and Therapeutic Applications.Hypertension (Dallas, Tex. : 1979) · 2025Review
- Potential molecular metabolic mechanisms underlying the effects of cimifugin in gastric cancer through single-cell and bulk RNA sequencing combined with network pharmacology.Journal of gastrointestinal oncology · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Modulation of cAMP/cGMP signaling as prevention of congenital heart defects in Pde2A deficient embryos: a matter of oxidative stress.Cell death & disease · 2024Article
- Scaffold Hopping and Optimization of Small Molecule Soluble Adenyl Cyclase Inhibitors Led by Free Energy Perturbation.Journal of chemical information and modeling · 2023Article
- Using the Proteomics Toolbox to Resolve Topology and Dynamics of Compartmentalized cAMP Signaling.International journal of molecular sciences · 2023Review
- Integrated analysis revealing a novel stemness-metabolism-related gene signature for predicting prognosis and immunotherapy response in hepatocellular carcinoma.Frontiers in immunology · 2023Article
- Dual viscosity mixture vehicle for intratympanic steroid treatment modifies the ROS and inflammation related proteomes.Frontiers in pharmacology · 2023Article
- Article
- Essential role of the mitochondrial NaCell reports · 2022Article
- A universal co-expression gene network and prognostic model for hepatic-biliary-pancreatic cancers identified by integrative analyses.FEBS open bio · 2022Article
- Abnormal Cyclic Nucleotide Signaling at the Outer Mitochondrial Membrane In Sympathetic Neurons During the Early Stages of Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Pharmacological Inhibition of Epac1 Averts Ferroptosis Cell Death by Preserving Mitochondrial Integrity.Antioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
cAMP/PKA signalling is compartmentalised with tight spatial and temporal control of signal propagation underpinning specificity of response. The cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within which they control local cAMP levels and are key regulators of signal compartmentalisation. Several components of the cAMP/PKA cascade are located to different mitochondrial sub-compartments, suggesting the presence of multiple cAMP/PKA signalling domains within the organelle. The function and regulation of these domains remain largely unknown. Here, we describe a novel cAMP/PKA signalling domain localised at mitochondrial membranes and regulated by PDE2A2. Using pharmacological and genetic approaches combined with real-time FRET imaging and high resolution microscopy, we demonstrate that in rat cardiac myocytes and other cell types mitochondrial PDE2A2 regulates local cAMP levels and PKA-dependent phosphorylation of Drp1. We further demonstrate that inhibition of PDE2A, by enhancing the hormone-dependent cAMP response locally, affects mitochondria dynamics and protects from apoptotic cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.