ArticlePloS one2012
Inhibition of CLIC4 enhances autophagy and triggers mitochondrial and ER stress-induced apoptosis in human glioma U251 cells under starvation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Construction and validation of a model based on necroptosis-related genes for predicting glioma prognosis.Discover oncology · 2026Article
- The role of chloride intracellular channel 4 in tumors.Cancer cell international · 2025Review
- Retrograde AAV-mediated gene modulation reveals chloride intracellular channel proteins as potent regulators of retinal ganglion cell death.Experimental neurology · 2024Article
- 14-3-3ε: a protein with complex physiology function but promising therapeutic potential in cancer.Cell communication and signaling : CCS · 2024Review
- Nucleo-cytoplasmic shuttling of 14-3-3 epsilon carrying hnRNP C promotes autophagy.Cancer biology & therapy · 2023Article
- Article
- Structure-based discovery and in vitro validation of inhibitors of chloride intracellular channel 4 protein.Computational and structural biotechnology journal · 2023Article
- CLIC4 localizes to mitochondrial-associated membranes and mediates cardioprotection.Science advances · 2022Article
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Morphology and composition of the midgut bacterial community of Scaptocoris castanea Perty, 1830 (Hemiptera: Cydnidae).Cell and tissue research · 2020Article
- Intracellular Chloride Channels: Novel Biomarkers in Diseases.Frontiers in physiology · 2020Review
- Resveratrol alleviates inflammatory injury and enhances the apoptosis of fibroblast‑like synoviocytes via mitochondrial dysfunction and ER stress in rats with adjuvant arthritis.Molecular medicine reports · 2019Article
- CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes of epithelial ovarian cancer.Scientific reports · 2018Article
- Detecting Protein Subcellular Localization by Green Fluorescence Protein Tagging and 4',6-Diamidino-2-phenylindole Staining in Caenorhabditis elegans.Journal of visualized experiments : JoVE · 2018Article
- Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro.Journal of visualized experiments : JoVE · 2018Article
- Article
- Ion channels in the regulation of autophagy.Autophagy · 2018Review
- 14-3-3ε is a nuclear matrix protein, and its altered expression and localization are associated with curcumin-induced apoptosis of MG-63 cells.Oncology letters · 2018Article
- Simvastatin Protects Heart from Pressure Overload Injury by Inhibiting Excessive Autophagy.International journal of medical sciences · 2018Article
- 14-3-3 proteins: an important regulator of autophagy in diseases.American journal of translational research · 2017Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to mitochondria, endoplasmic reticulum (ER), nucleus and cytoplasm, and participates in the apoptotic response to stress. Apoptosis and autophagy, the main types of the programmed cell death, seem interconnected under certain stress conditions. However, the role of CLIC4 in autophagy regulation has yet to be determined. In this study, we demonstrate upregulation and nuclear translocation of the CLIC4 protein following starvation in U251 cells. CLIC4 siRNA transfection enhanced autophagy with increased LC3-II protein and puncta accumulation in U251 cells under starvation conditions. In that condition, the interaction of the 14-3-3 epsilon isoform with CLIC4 was abolished and resulted in Beclin 1 overactivation, which further activated autophagy. Moreover, inhibiting the expression of CLIC4 triggered both mitochondrial apoptosis involved in Bax/Bcl-2 and cytochrome c release under starvation and endoplasmic reticulum stress-induced apoptosis with CHOP and caspase-4 upregulation. These results demonstrate that CLIC4 nuclear translocation is an integral part of the cellular response to starvation. Inhibiting the expression of CLIC4 enhances autophagy and contributes to mitochondrial and ER stress-induced apoptosis under starvation.
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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.