ArticleCellular and molecular life sciences : CMLS2017
Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure.
Article in Cellular and molecular life sciences : CMLS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 243 papers, 2 of them syntheses that pooled it.
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Who cites it
243 citing papers in PubMed, 2 syntheses or guidelines pooled it, 357 citations in OpenAlex.
- Ferroptosis and ferritinophagy in diabetes complications.Molecular metabolism · 2022Pooled it
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- Integrative transcriptomic and single-cell analyses identify CD74 as a candidate regulator of ferroptosis in renal tubular cells during nephrolithiasis.Renal failure · 2026Article
- The kinase domain of RIPK3 tunes its scaffolding functions.Cell death and differentiation · 2026Article
- Molecular mechanisms of iron metabolism and ferroptosis in cardiovascular diseases and intervention strategies targeting natural products (Review).Molecular medicine reports · 2026Review
- Integrated Necroptosis Within Programmed Cell Death in Traumatic Brain Injury.Molecular neurobiology · 2026Review
- MLKL confers ferroptosis resistance in colorectal cancer cells via impaired ESCRT-III-mediated membrane repair.Biology direct · 2026Article
- Dapagliflozin attenuates ferroptosis in diabetic nephropathy through activation of the Nrf2/HO‑1 signaling pathway.International journal of molecular medicine · 2026Article
- Review
- Therapeutic and mechanistic insights on mitochondrial transplantation in kidney disease.Nature reviews. Nephrology · 2026Review
- Clinical implications of ferroptosis in critical illness: a narrative review.Journal of intensive care · 2026Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting Ferroptosis and Necroptosis to Treat Stroke.Neurochemical research · 2026Review
- Small molecules targeting regulated cell death for chronic kidney disease therapy.Journal of pharmaceutical analysis · 2026Review
- IFI16 is essential to linking DNA damage and ferroptosis in acute kidney injury.Cell death & disease · 2026Article
- Cross-talk among novel programmed cell death pathways: a decisive network in renal ischemia-reperfusion injury.Frontiers in immunology · 2026Review
- The Regulatory Landscape of Ferroptosis and Iron Homeostasis: Pathophysiological Mechanisms and Therapeutic Horizons in Cardiovascular Disease.Drug design, development and therapy · 2026Review
- Targeting Programmed Cell Death in Depression: A Review of Traditional Chinese Medicine Interventions Based on Preclinical Evidence.Neuropsychiatric disease and treatment · 2026Review
- Ferroptosis and Alzheimer's disease: a new insight into neurodegeneration.Frontiers in immunology · 2026Review
- SP1 Aggravates Neonatal Hypoxic-Ischemic Brain Damage by Promoting Ferroptosis Through Transcriptional Upregulation of ACSL4.ASN neuro · 2026Article
183 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Ferroptosis is a recently recognized caspase-independent form of regulated cell death that is characterized by the accumulation of lethal lipid ROS produced through iron-dependent lipid peroxidation. Considering that regulation of fatty acid metabolism is responsible for the membrane-resident pool of oxidizable fatty acids that undergo lipid peroxidation in ferroptotic processes, we examined the contribution of the key fatty acid metabolism enzyme, acyl-CoA synthetase long-chain family member 4 (ACSL4), in regulating ferroptosis. By using CRISPR/Cas9 technology, we found that knockout of Acsl4 in ferroptosis-sensitive murine and human cells conferred protection from erastin- and RSL3-induced cell death. In the same cell types, deletion of mixed lineage kinase domain-like (Mlkl) blocked susceptibility to necroptosis, as expected. Surprisingly, these studies also revealed ferroptosis and necroptosis are alternative, in that resistance to one pathway sensitized cells to death via the other pathway. These data suggest a mechanism by which one regulated necrosis pathway compensates for another when either ferroptosis or necroptosis is compromised. We verified the synergistic contributions of ferroptosis and necroptosis to tissue damage during acute organ failure in vivo. Interestingly, in the course of pathophysiological acute ischemic kidney injury, ACSL4 was initially upregulated and its expression level correlated with the severity of tissue damage. Together, our findings reveal ACSL4 to be a reliable biomarker of the emerging cell death modality of ferroptosis, which may also serve as a novel therapeutic target in preventing pathological cell death processes.
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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.