ArticleFree radical biology & medicine2021
Disrupting CISD2 function in cancer cells primarily impacts mitochondrial labile iron levels and triggers TXNIP expression.
Article in Free radical biology & medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Ferroptosis and ferritinophagy in diabetes complications.Molecular metabolism · 2022Pooled it
- Immunogenic cell death: synergizing ferroptosis and cuproptosis to overcome immunotherapy resistance.Medical oncology (Northwood, London, England) · 2026Review
- Genetic mutations governing ferroptosis sensitivity and resistance: a precision approach to cancer therapy.Cell death & disease · 2026Review
- Exploration of the Regulatory Network of Programmed Cell Death Genes in Rheumatoid Arthritis Based on Blood-Derived circRNA Transcriptome Information and Single-Cell Multi-omics Data.Biochemical genetics · 2025Article
- CISD2 ensures adequate ER-mitochondrial coupling, critically supporting mitochondrial function in neurons.Acta neuropathologica communications · 2025Article
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
- Construction of a prognostic model based on ferroptosis- and mitochondrial metabolism-related genes for patients with breast cancer.Medicine · 2025Article
- The Labile Side of Iron in Health and Disease: A Narrative Review.Advances in experimental medicine and biology · 2025Review
- Article
- CircSLC25A16 facilitates the development of non-small-cell lung cancer through the miR-335-5p/CISD2 axis.Thoracic cancer · 2024Article
- CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Inhibition of CISD2 enhances sensitivity to doxorubicin in diffuse large B-cell lymphoma by regulating ferroptosis and ferritinophagy.Frontiers in pharmacology · 2024Article
- The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control.British journal of cancer · 2023Review
- Targeting Iron-Sulfur Clusters in Cancer: Opportunities and Challenges for Ferroptosis-Based Therapy.Cancers · 2023Review
- Ferroptosis regulates key signaling pathways in gastrointestinal tumors: Underlying mechanisms and therapeutic strategies.World journal of gastroenterology · 2023Review
- Nature-Inspired Bioactive Compounds: A Promising Approach for Ferroptosis-Linked Human Diseases?Molecules (Basel, Switzerland) · 2023Review
- Identification of iron metabolism-related genes as diagnostic signatures in sepsis by blood transcriptomic analysis.Open life sciences · 2023Article
- Immunomodulatory Role of Thioredoxin Interacting Protein in Cancer's Impediments: Current Understanding and Therapeutic Implications.Vaccines · 2022Review
- The Cluster Transfer Function of AtNEET Supports the Ferredoxin-Thioredoxin Network of Plant Cells.Antioxidants (Basel, Switzerland) · 2022Article
- A peptide-derived strategy for specifically targeting the mitochondria and ER of cancer cells: a new approach in fighting cancer.Chemical science · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The CISD2 (NAF-1) protein plays a key role in regulating cellular homeostasis, aging, cancer and neurodegenerative diseases. It was found to control different calcium, reactive oxygen species (ROS), and iron signaling mechanisms. However, since most studies of CISD2 to date were conducted with cells that constitutively lack, overexpress, or contain mutations in CISD2, the relationships between these different signaling processes are unclear. To address the hierarchy of signaling events occurring in cells upon CISD2 disruption, we developed an inducible system to express CISD2, or the dominant-negative H114C inhibitor of CISD2, in human breast cancer cells. Here, we report that inducible disruption of CISD2 function causes an immediate disruption in mitochondrial labile iron (mLI), and that this disruption results in enhanced mitochondrial ROS (mROS) levels. We further show that alterations in cytosolic and ER calcium levels occur only after the changes in mLI and mROS levels happen and are unrelated to them. Interestingly, disrupting CISD2 function resulted in the enhanced expression of the tumor suppressor thioredoxin-interacting protein (TXNIP) that was dependent on the accumulation of mLI and associated with ferroptosis activation. CISD2 could therefore regulate the expression of TXNIP in cancer cells, and this regulation is dependent on alterations in mLI levels.
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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.