ArticleCell death & disease2021
Cyclic AMP-binding protein Epac1 acts as a metabolic sensor to promote cardiomyocyte lipotoxicity.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- Inhibition of EPAC1 Prevents Neuronal Death Mediated by Diesel Exhaust Particles in Ferroptotic Cell Death Conditions.Antioxidants (Basel, Switzerland) · 2026Article
- Cannabidiol does not cause DNA double-strand breaks in a human liver-derived cell model.Journal of cannabis research · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Semaphorin-3A regulates liver sinusoidal endothelial cell porosity and promotes hepatic steatosis.Nature cardiovascular research · 2024Article
- The role of soluble adenylyl cyclase in sensing and regulating intracellular pH.Pflugers Archiv : European journal of physiology · 2024Review
- Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation.Biochemical Society transactions · 2024Article
- Endothelin receptor antagonists (ERAs) can potentially be used as therapeutic drugs to reduce hypertension caused by small molecule tyrosine kinase inhibitors (TKIs).Frontiers in pharmacology · 2024Review
- Microvascular rarefaction caused by the NOTCH signaling pathway is a key cause of TKI-apatinib-induced hypertension and cardiac damage.Frontiers in pharmacology · 2024Review
- Mechanism ofFrontiers in pharmacology · 2024Article
- Tripterygium glycosides improve abnormal lipid deposition in nephrotic syndrome rat models.Renal failure · 2023Article
- Energy Regulation in Inflammatory Sarcopenia by the Purinergic System.International journal of molecular sciences · 2023Review
- Article
- Growth arrest and DNA damage-inducible alpha regulates muscle repair and fat infiltration through ATP synthase F1 subunit alpha.Journal of cachexia, sarcopenia and muscle · 2023Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Cyclic adenosine monophosphate (cAMP) is a master regulator of mitochondrial metabolism but its precise mechanism of action yet remains unclear. Here, we found that a dietary saturated fatty acid (FA), palmitate increased intracellular cAMP synthesis through the palmitoylation of soluble adenylyl cyclase in cardiomyocytes. cAMP further induced exchange protein directly activated by cyclic AMP 1 (Epac1) activation, which was upregulated in the myocardium of obese patients. Epac1 enhanced the activity of a key enzyme regulating mitochondrial FA uptake, carnitine palmitoyltransferase 1. Consistently, pharmacological or genetic Epac1 inhibition prevented lipid overload, increased FA oxidation (FAO), and protected against mitochondrial dysfunction in cardiomyocytes. In addition, analysis of Epac1 phosphoproteome led us to identify two key mitochondrial enzymes of the the β-oxidation cycle as targets of Epac1, the long-chain FA acyl-CoA dehydrogenase (ACADL) and the 3-ketoacyl-CoA thiolase (3-KAT). Epac1 formed molecular complexes with the Ca
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