ArticleCell communication and signaling : CCS2018
AMPK-dependent and independent actions of P2X7 in regulation of mitochondrial and lysosomal functions in microglia.
Article in Cell communication and signaling : CCS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 72 citations in OpenAlex.
- Energy Homeostasis Disruption in Neurological Disorders: Mitochondrial Dysfunction, High-Energy Phosphate Transfer, and Extracellular ATP-Dependent Purinergic Dysregulation.International journal of molecular sciences · 2026Review
- AMPK-NLRP3 Inflammasome Crosstalk: Structural Insights, Molecular Mechanisms, and Therapeutic Implications for Inflammation and Neuroinflammation.Molecular neurobiology · 2026Review
- Neuroinflammatory control of metabolism in huntington's disease: central role of P2 × 7 receptor mediated redox lipid/epigenetic crosstalk.Inflammopharmacology · 2026Review
- P2X7 receptor-dependent microglia-astrocyte coupling in Alzheimer's disease: from eATP sensing to synaptic and proteostatic failure.Frontiers in aging neuroscience · 2026Review
- P2X7 Receptor in Rare Diseases: Shared Molecular Mechanisms and Therapeutic Implications.Journal of inflammation research · 2026Review
- Multiple Mechanisms and Therapeutic Strategies for the Involvement of AMPK in the Development of Alzheimer's Disease.Molecular neurobiology · 2025Review
- High-Power Laser Therapy Modulates Mitochondrial Function and Redox Balance Without Cytotoxicity: An In Vitro Study in BV-2 Microglial Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- The Multifaceted Role of P2X7R in Microglia and Astrocytes.Neurochemical research · 2025Review
- Inhibition of USP30 Promotes Mitophagy by Regulating Ubiquitination of MFN2 by Parkin to Attenuate Early Brain Injury After SAH.Translational stroke research · 2025Article
- Protein disulfide isomerase integrates toll-like receptor 4 and P2X7 receptor signaling pathways during lipopolysaccharide-induced neuroinflammation.Scientific reports · 2025Article
- A narrative review of autophagy in migraine.Frontiers in neuroscience · 2025Review
- Druggable targets for Parkinson's disease: transcriptomics based Mendelian randomization study.Scientific reports · 2024Article
- Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.bioRxiv : the preprint server for biology · 2024Article
- Implications of COVID-19 in Parkinson's disease: the purinergic system in a therapeutic-target perspective to diminish neurodegeneration.Purinergic signalling · 2024Review
- P2X7 Receptor: an Emerging Target in Alzheimer's Disease.Molecular neurobiology · 2024Review
- NLRX1 Inhibits LPS-Induced Microglial Death via Inducing p62-Dependent HO-1 Expression, Inhibiting MLKL and Activating PARP-1.Antioxidants (Basel, Switzerland) · 2024Article
- CASK Mediates Oxidative Stress-Induced Microglial Apoptosis-Inducing Factor-Independent Parthanatos Cell Death via Promoting PARP-1 Hyperactivation and Mitochondrial Dysfunction.Antioxidants (Basel, Switzerland) · 2024Article
- Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy.World journal of clinical oncology · 2023Review
- Spatiotemporal roles of AMPK in PARP-1- and autophagy-dependent retinal pigment epithelial cell death caused by UVA.Journal of biomedical science · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundP2X7 is ubiquitously expressed in myeloid cells and regulates the pathophysiology of inflammatory diseases. Since mitochondrial function in microglia is highly associated with microglial functions in controlling neuronal plasticity and brain homeostasis, we interested to explore the roles of P2X7 in mitochondrial and lysosomal functions as well as mitophagy in microglia.
methodsP2X7
resultsIn primary microglia, BV-2 microglial cells and BMDM, P2X7 agonist BzATP triggered AMPK activation and LC3II accumulation through reactive oxygen species (ROS) and CaMKKII pathways, and these effects were abolished by P2X7 antagonist A438079 and P2X7 deficiency. Moreover, we detected the dramatic decreases of mitochondrial OCR and mass following P2X7 activation. AMPK inhibition by compound C or AMPK silencing reversed the P2X7 actions in reduction of mitochondrial mass, induction of mitochondrial fission and mitophagy, but not in uncoupling of mitochondrial respiration. Interestingly, we found that P2X7 activation induced nuclear translocation of TFEB via an AMPK-dependent pathway and led to lysosomal biogenesis. Mimicking the actions of BzATP, nigericin also induced ROS-dependent AMPK activation, mitophagy, mitochondrial fission and respiratory inhibition. Longer exposure of BzATP induced cell death, and this effect was accompanied by the lysosomal instability and was inhibited by autophagy and cathepsin B inhibitors.
conclusionAltogether ROS- and CaMKK-dependent AMPK activation is involved in P2X7-mediated mitophagy, mitochondrial dynamics and lysosomal biogenesis in microglial cells, which is followed by cytotoxicity partially resulting from mitophagy and cathepsin B activation.
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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.