ArticleAutophagy2015
Autophagy of metallothioneins prevents TNF-induced oxidative stress and toxicity in hepatoma cells.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy.Materials today. Bio · 2025Article
- Adaptation in the Alleyways: Candidate Genes Under Potential Selection in Urban Coyotes.Genome biology and evolution · 2025Article
- Metallothionein-3 is a multifunctional driver that modulates the development of sorafenib-resistant phenotype in hepatocellular carcinoma cells.Biomarker research · 2024Article
- Transcriptomic screening of novel targets of sericin in human hepatocellular carcinoma cells.Scientific reports · 2024Article
- Autophagy in Cancer Immunotherapy.Cells · 2022Review
- Review
- Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line.International journal of molecular sciences · 2022Article
- Metallothionein 2A (MT2A) controls cell proliferation and liver metastasis by controlling the MST1/LATS2/YAP1 signaling pathway in colorectal cancer.Cancer cell international · 2022Article
- Integrated Analysis of mRNA and lncRNA Expression Profiles Reveals Regulatory Networks Associated with Decompensated Cirrhosis.Journal of immunology research · 2022Article
- Research progress of nano selenium in the treatment of oxidative stress injury during hepatic ischemia-reperfusion injury.Frontiers in pharmacology · 2022Review
- ACO1 and IREB2 downregulation confer poor prognosis and correlate with autophagy-related ferroptosis and immune infiltration in KIRC.Frontiers in oncology · 2022Article
- Autophagy Triggers Tamoxifen Resistance in Human Breast Cancer Cells by Preventing Drug-Induced Lysosomal Damage.Cancers · 2021Article
- Construction of a competitive endogenous RNA network and analysis of potential regulatory axis targets in glioblastoma.Cancer cell international · 2021Article
- Integrative Analysis of Metallothioneins Identifies MT1H as Candidate Prognostic Biomarker in Hepatocellular Carcinoma.Frontiers in molecular biosciences · 2021Article
- ATIC inhibits autophagy in hepatocellular cancer through the AKT/FOXO3 pathway and serves as a prognostic signature for modeling patient survival.International journal of biological sciences · 2021Article
- lncRNA STEAP3-AS1 Modulates Cell Cycle Progression via Affecting CDKN1C Expression through STEAP3 in Colon Cancer.Molecular therapy. Nucleic acids · 2020Article
- Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition.International journal of molecular sciences · 2020Review
- The crosstalk between autophagy and ferroptosis: what can we learn to target drug resistance in cancer?Cancer biology & medicine · 2019Article
- The relationship between autophagy and the immune system and its applications for tumor immunotherapy.Molecular cancer · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomal membrane permeabilization (LMP) induced by oxidative stress has recently emerged as a prominent mechanism behind TNF cytotoxicity. This pathway relies on diffusion of hydrogen peroxide into lysosomes containing redox-active iron, accumulated by breakdown of iron-containing proteins and subcellular organelles. Upon oxidative lysosomal damage, LMP allows relocation to the cytoplasm of low mass iron and acidic hydrolases that contribute to DNA and mitochondrial damage, resulting in death by apoptosis or necrosis. Here we investigate the role of lysosomes and free iron in death of HTC cells, a rat hepatoma line, exposed to TNF following metallothionein (MT) upregulation. Iron-binding MT does not normally occur in HTC cells in significant amounts. Intracellular iron chelation attenuates TNF and cycloheximide (CHX)-induced LMP and cell death, demonstrating the critical role of this transition metal in mediating cytokine lethality. MT upregulation, combined with starvation-activated MT autophagy almost completely suppresses TNF and CHX toxicity, while impairment of both autophagy and MT upregulation by silencing of Atg7, and Mt1a and/or Mt2a, respectively, abrogates protection. Interestingly, MT upregulation by itself has little effect, while stimulated autophagy alone depresses cytokine toxicity to some degree. These results provide evidence that intralysosomal iron-catalyzed redox reactions play a key role in TNF and CHX-induced LMP and toxicity. The finding that chelation of intralysosomal iron achieved by autophagic delivery of MT, and to some degree probably of other iron-binding proteins as well, into the lysosomal compartment is highly protective provides a putative mechanism to explain autophagy-related suppression of death by TNF and CHX.
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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.