ArticleProceedings of the National Academy of Sciences of the United States of America2024
RIPK4 promotes oxidative stress and ferroptotic death through the downregulation of ACSM1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Herbal Interventions in Parkinson's Disease: A Systematic Review of Preclinical Studies.Cellular and molecular neurobiology · 2025Pooled it
- Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026Review
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.eLife · 2026Article
- An Integrated DNA Nanoprobe for Intranuclear Imaging and In Situ Profiling of OGG1 Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial dysfunction in peri-implantitis: bioinformatics and machine learning analysis with in vivo experiment.Odontology · 2026Article
- Revealing improvement mechanism of yak meat quality by dietary withFood chemistry. Molecular sciences · 2026Article
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.bioRxiv : the preprint server for biology · 2026Article
- Unraveling the synergy of inflammation and apoptosis in sepsis-induced acute lung injury: Insights and therapeutic perspectives (Review).Molecular medicine reports · 2026Review
- The Interaction Between Ferroptosis and Necroptosis in Acute and Chronic Kidney Diseases.Journal of inflammation research · 2026Review
- Bibliometric and visual analysis of ferroptosis in cardiovascular diseases.Journal of cardiothoracic surgery · 2025Review
- Regulatory Landscapes of Protein Acylations in Neuroinflammation: From Molecular Mechanisms to Therapeutic Targets.Neurochemical research · 2025Review
- RIPK4-mediated MFN2 degradation drives osteogenesis through mitochondrial fragmentation and restricts myelopoiesis by blocking mitochondrial transfer.Nature communications · 2025Article
- Irisin prevents liver injury during exhausting physical activity by suppressing ferroptosis via Nrf2/GPX4 signaling.BMC gastroenterology · 2025Article
- LLMs and AI Life Models for Traditional Chinese Medicine-derived Geroprotector Formulation.Aging and disease · 2025Article
- Ferroptosis in ischemia-reperfusion injury: molecular mechanisms and therapeutic strategies.American journal of cardiovascular disease · 2025Review
- RIPK4 promotes oxidative stress and ferroptotic death through the downregulation of ACSM1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
10 authors.
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Abstract
One of the most critical axes for cell fate determination is how cells respond to excessive reactive oxygen species (ROS)-oxidative stress. Extensive lipid peroxidation commits cells to death via a distinct cell death paradigm termed ferroptosis. However, the molecular mechanism regulating cellular fates to distinct ROS remains incompletely understood. Through siRNA against human receptor-interacting protein kinase (RIPK) family members, we found that RIPK4 is crucial for oxidative stress and ferroptotic death. Upon ROS induction, RIPK4 is rapidly activated, and the kinase activity of RIPK4 is indispensable to induce cell death. Specific ablation of RIPK4 in kidney proximal tubules protects mice from acute kidney injury induced by cisplatin and renal ischemia/reperfusion. RNA sequencing revealed the dramatically decreased expression of acyl-CoA synthetase medium-chain (ACSM) family members induced by cisplatin treatment which is compromised in RIPK4-deficient mice. Among these ACSM family members, suppression of ACSM1 strongly augments oxidative stress and ferroptotic cell death with induced expression of ACS long-chain family member 4, an important component for ferroptosis execution. Our lipidome analysis revealed that overexpression of ACSM1 leads to the accumulation of monounsaturated fatty acids, attenuation of polyunsaturated fatty acid (PUFAs) production, and thereby cellular resistance to ferroptosis. Hence, knockdown of ACSM1 resensitizes RIPK4 KO cells to oxidative stress and ferroptotic death. In conclusion, RIPK4 is a key player involved in oxidative stress and ferroptotic death, which is potentially important for a broad spectrum of human pathologies. The link between the RIPK4-ASCM1 axis to PUFAs and ferroptosis reveals a unique mechanism to oxidative stress-induced necrosis and ferroptosis.
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