Regulation of AMPK activity by type 10 adenylyl cyclase: contribution to the mitochondrial biology, cellular redox and energy homeostasis
| العنوان: | Regulation of AMPK activity by type 10 adenylyl cyclase: contribution to the mitochondrial biology, cellular redox and energy homeostasis |
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| المؤلفون: | Vera Regitz-Zagrosek, Vignesh Jayarajan, Yury Ladilov, Avinash Appukuttan, Muhammad Aslam, Peter H Reusch |
| المصدر: | Cellular and Molecular Life Sciences. 76:4945-4959 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | AMPK, Mitochondrial ROS, Biochemistry & Molecular Biology, 0601 Biochemistry and Cell Biology, ADCY10, Cell Physiological Phenomena, Adenylyl cyclase, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, AMP-Activated Protein Kinase Kinases, cAMP, Mitophagy, Cyclic AMP, Animals, Guanine Nucleotide Exchange Factors, Homeostasis, Humans, Myocytes, Cardiac, Phosphorylation, education, Protein kinase A, Molecular Biology, Pharmacology, 0303 health sciences, education.field_of_study, 030302 biochemistry & molecular biology, Endothelial Cells, ROS, 1103 Clinical Sciences, Cell Biology, Soluble adenylyl cyclase, 0606 Physiology, Mitochondria, Rats, Cell biology, ATP, Mitochondrial biogenesis, chemistry, Molecular Medicine, Energy Metabolism, Oxidation-Reduction, Protein Kinases, Adenylyl Cyclases |
| الوصف: | The downregulation of AMP-activated protein kinase (AMPK) activity contributes to numerous pathologies. Recent reports suggest that the elevation of cellular cAMP promotes AMPK activity. However, the source of the cAMP pool that controls AMPK activity remains unknown. Mammalian cells possess two cAMP sources: membrane-bound adenylyl cyclase (tmAC) and intracellularly localized, type 10 soluble adenylyl cyclase (sAC). Due to the localization of sAC and AMPK in similar intracellular compartments, we hypothesized that sAC may control AMPK activity. In this study, sAC expression and activity were manipulated in H9C2 cells, adult rat cardiomyocytes or endothelial cells. sAC knockdown depleted the cellular cAMP content and decreased AMPK activity in an EPAC-dependent manner. Functionally, sAC knockdown reduced cellular ATP content, increased mitochondrial ROS formation and led to mitochondrial depolarization. Furthermore, sAC downregulation led to EPAC-dependent mitophagy disturbance, indicated by an increased mitochondrial mass and unaffected mitochondrial biogenesis. Consistently, sAC overexpression or stimulation with bicarbonate significantly increased AMPK activity and cellular ATP content. In contrast, tmAC inhibition or stimulation produced no effect on AMPK activity. Therefore, the sAC-EPAC axis may regulate basal and induced AMPK activity and support mitophagy, cellular energy and redox homeostasis. The study argues for sAC as a potential target in treating pathologies associated with AMPK downregulation. |
| تدمد: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-019-03152-y |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a31d00c010e13ff0f7c9a44ba4a0c447 https://doi.org/10.1007/s00018-019-03152-y |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a31d00c010e13ff0f7c9a44ba4a0c447 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14209071 1420682X |
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| DOI: | 10.1007/s00018-019-03152-y |