ArticleAutophagy2016
Mechanistic study of TRPM2-Ca(2+)-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Pooled it
- The TRPM2-PARP-1 Axis Involvement in Bisphenol A and Nonylphenol-Induced Ferroptosis in Trigeminal Ganglion Cells.Journal of applied toxicology : JAT · 2026Article
- Dietary Arginine Supplementation Mitigates Heat Stress-Induced Testicular Dysfunction Through Arginine-Related Metabolic Remodeling and Autophagy-Associated Stress Adaptation in a Rongchang Boar Model.Animals : an open access journal from MDPI · 2026Article
- Article
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- Article
- Upregulated TRPM1 is associated with apoptosis in Rs1 knockout mice and in ARPE19 cells through increased intracellular calcium.Scientific reports · 2026Article
- Calcium imbalance drives organelle network collapse and immune remodeling: novel pathogenic mechanisms in MASLD progression.Frontiers in immunology · 2026Review
- PARP1-TRPM2-PKC cascade distinctly regulates reactive astrogliosis and clasmatodendrosis through NF-κB and AKT pathways in the hippocampus of chronic epilepsy rats.Scientific reports · 2025Article
- Oxidative Stress in the Regulation of Autosis-Related Proteins.Antioxidants (Basel, Switzerland) · 2025Review
- NSP6 regulates calcium overload-induced autophagic cell death and is regulated by KLHL22-mediated ubiquitination.Journal of advanced research · 2025Article
- TRPM2 channels mediate ROS-induced actin remodeling and cell migration of prostate cancer cells.BMC cancer · 2025Article
- The Protective Effect of Annexin A1 on Autophagy Via the CAMK2/BECN1 Signaling Pathway in PC12 Cells Stimulated with HNeurotoxicity research · 2025Article
- TRP channels and breast cancer: the role of TRPs in the pathophysiological development.Frontiers in molecular biosciences · 2025Review
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- TRPM channels in human cancers: regulatory mechanism and therapeutic prospects.Biomarker research · 2024Review
- Bis-benzylisoquinoline alkaloids inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy.Virologica Sinica · 2024Article
- Inhibition of STIM1 alleviates high glucose-induced proliferation and fibrosis by inducing autophagy in mesangial cells.Molecular and cellular biochemistry · 2024Article
- Article
- TLR4 induced TRPM2 mediated neuropathic pain.Frontiers in pharmacology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reactive oxygen species (ROS) have been commonly accepted as inducers of autophagy, and autophagy in turn is activated to relieve oxidative stress. Yet, whether and how oxidative stress, generated in various human pathologies, regulates autophagy remains unknown. Here, we mechanistically studied the role of TRPM2 (transient receptor potential cation channel subfamily M member 2)-mediated Ca(2+) influx in oxidative stress-mediated autophagy regulation. On the one hand, we demonstrated that oxidative stress triggered TRPM2-dependent Ca(2+) influx to inhibit the induction of early autophagy, which renders cells more susceptible to death. On the other hand, oxidative stress induced autophagy (and not cell death) in the absence of the TRPM2-mediated Ca(2+) influx. Moreover, in response to oxidative stress, TRPM2-mediated Ca(2+) influx activated CAMK2 (calcium/calmodulin dependent protein kinase II) at levels of both phosphorylation and oxidation, and the activated CAMK2 subsequently phosphorylated BECN1/Beclin 1 on Ser295. Ser295 phosphorylation of BECN1 in turn decreased the association between BECN1 and PIK3C3/VPS34, but induced binding between BECN1 and BCL2. Clinically, acetaminophen (APAP) overdose is the most common cause of acute liver failure worldwide. We demonstrated that APAP overdose also activated ROS-TRPM2-CAMK2-BECN1 signaling to suppress autophagy, thereby causing primary hepatocytes to be more vulnerable to death. Inhibiting the TRPM2-Ca(2+)-CAMK2 cascade significantly mitigated APAP-induced liver injury. In summary, our data clearly demonstrate that oxidative stress activates the TRPM2-Ca(2+)-CAMK2 cascade to phosphorylate BECN1 resulting in autophagy inhibition.
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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.