Ferroptosis: molecular mechanisms and health implications

Cell Research, Journal Year: 2020, Volume and Issue: 31(2), P. 107 - 125

Published: Dec. 2, 2020

Abstract Cell death can be executed through different subroutines. Since the description of ferroptosis as an iron-dependent form non-apoptotic cell in 2012, there has been mounting interest process and function ferroptosis. Ferroptosis occur two major pathways, extrinsic or transporter-dependent pathway intrinsic enzyme-regulated pathway. is caused by a redox imbalance between production oxidants antioxidants, which driven abnormal expression activity multiple redox-active enzymes that produce detoxify free radicals lipid oxidation products. Accordingly, precisely regulated at levels, including epigenetic, transcriptional, posttranscriptional posttranslational layers. The transcription factor NFE2L2 plays central role upregulating anti-ferroptotic defense, whereas selective autophagy may promote ferroptotic death. Here, we review current knowledge on integrated molecular machinery describe how dysregulated involved cancer, neurodegeneration, tissue injury, inflammation, infection.

Language: Английский

---

Broadening horizons: the role of ferroptosis in cancer

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(5), P. 280 - 296

Published: Jan. 29, 2021

Language: Английский

---

Ferroptosis: machinery and regulation

Autophagy, Journal Year: 2020, Volume and Issue: 17(9), P. 2054 - 2081

Published: Aug. 19, 2020

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which controlled integrated oxidation and antioxidant systems. The iron-containing enzyme lipoxygenase the main promoter ferroptosis producing hydroperoxides, its function relies on activation ACSL4-dependent biosynthesis. In contrast, selenium-containing GPX4 currently recognized as a central repressor ferroptosis, activity depends glutathione produced from cystine-glutamate antiporter SLC7A11. Many metabolic (especially involving iron, lipids, amino acids) degradation pathways (macroautophagy/autophagy ubiquitin-proteasome system) orchestrate complex ferroptotic response through direct or indirect regulation iron accumulation peroxidation. Although detailed mechanism membrane injury during remains mystery, ESCRT III-mediated plasma repair can make cells resistant to ferroptosis. Here, we review recent rapid progress in understanding molecular mechanisms focus epigenetic, transcriptional, posttranslational this process.Abbreviations: 2ME: beta-mercaptoethanol; α-KG: α-ketoglutarate; ccRCC: clear renal carcinoma; EMT: epithelial-mesenchymal transition; FAO: fatty acid beta-oxidation; GSH: glutathione; MEFs: mouse embryonic fibroblasts; MUFAs: monounsaturated acids; NO: nitric oxide; NOX: NADPH oxidase; PPP: pentose phosphate pathway; PUFA: polyunsaturated acid; RCD: death; RNS: reactive nitrogen species; ROS: oxygen RTAs: radical-trapping antioxidants; UPS: system; UTR: untranslated region.

Language: Английский

---

Autophagy in major human diseases

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(19)

Published: Aug. 30, 2021

Review30 August 2021Open Access Autophagy in major human diseases Daniel J Klionsky orcid.org/0000-0002-7828-8118 Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA Search for more papers by this author Giulia Petroni Department Radiation Oncology, Weill Cornell Medical College, New York, NY, Ravi K Amaravadi Medicine, Pennsylvania, Philadelphia, PA, Abramson Cancer Center, Eric H Baehrecke Molecular, Cell and Biology, Massachusetts School, Worcester, MA, Andrea Ballabio orcid.org/0000-0003-1381-4604 Telethon Institute Genetics Pozzuoli, Italy Translational Sciences, Section Pediatrics, Federico II University, Naples, Molecular Human Genetics, Baylor College Jan Dan Duncan Neurological Research Texas Children Hospital, Houston, TX, Patricia Boya orcid.org/0000-0003-3045-951X Margarita Salas Center Biological Research, Spanish National Council, Madrid, Spain José Manuel Bravo-San Pedro Faculty Physiology, Complutense Networked Biomedical Neurodegenerative Diseases (CIBERNED), Ken Cadwell Kimmel Biology Medicine at the Skirball York Grossman School Microbiology, Division Gastroenterology Hepatology, Langone Health, Francesco Cecconi orcid.org/0000-0002-5614-4359 Stress Survival Unit, Autophagy, Recycling Disease (CARD), Danish Society Copenhagen, Denmark Pediatric Onco-Hematology Gene Therapy, IRCCS Bambino Gesù Children's Rome, Rome 'Tor Vergata', Augustine M Choi Pulmonary Critical Care Joan Sanford I. York-Presbyterian Mary E Nephrology Hypertension, Charleen T Chu orcid.org/0000-0002-5052-8271 Pathology, Pittsburgh Pittsburgh, Patrice Codogno orcid.org/0000-0002-5492-3180 Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Paris, France Université de Maria Isabel Colombo Laboratorio Mecanismos Moleculares Implicados en el Tráfico Vesicular y la Autofagia-Instituto Histología Embriología (IHEM)-Universidad Nacional Cuyo, CONICET- Facultad Ciencias Médicas, Mendoza, Argentina Ana Cuervo orcid.org/0000-0002-0771-700X Developmental Albert Einstein Bronx, Aging Studies, Vojo Deretic Inflammation Metabolism (AIM, Excellence, Mexico Health Albuquerque, NM, Ivan Dikic orcid.org/0000-0001-8156-9511 Biochemistry II, Goethe Frankfurt, Frankfurt am Main, Germany Buchmann Zvulun Elazar Biomolecular The Weizmann Science, Rehovot, Israel Eeva-Liisa Eskelinen Biomedicine, Turku, Finland Gian Fimia orcid.org/0000-0003-4438-3325 Sapienza Epidemiology, Preclinical Advanced Diagnostics, Infectious 'L. Spallanzani' IRCCS, David A Gewirtz orcid.org/0000-0003-0437-4934 Pharmacology Toxicology, Virginia Commonwealth Richmond, VA, Douglas R Green Immunology, St. Jude Memphis, TN, Malene Hansen Burnham Prebys Discovery Program Development, Aging, Regeneration, La Jolla, CA, Marja Jäättelä orcid.org/0000-0001-5950-7111 Death Metabolism, & Disease, Cellular Terje Johansen orcid.org/0000-0003-1451-9578 Group, Tromsø—The Arctic Norway, Tromsø, Norway Gábor Juhász Szeged, Hungary Anatomy, Eötvös Loránd Budapest, Vassiliki Karantza Merck Co., Inc., Kenilworth, NJ, Claudine Kraft orcid.org/0000-0002-3324-4701 ZBMZ, Freiburg, CIBSS - Centre Integrative Signalling Guido Kroemer orcid.org/0000-0002-9334-4405 Recherche des Cordeliers, Equipe Labellisée par Ligue Contre le Cancer, Sorbonne Université, Inserm U1138, Universitaire France, Metabolomics Platforms, Gustave Roussy, Villejuif, Pôle Biologie, Hôpital Européen Georges Pompidou, AP-HP, Suzhou Systems Chinese Academy Suzhou, China Karolinska Women's Stockholm, Sweden Nicholas Ktistakis Programme, Babraham Cambridge, UK Sharad Kumar orcid.org/0000-0001-7126-9814 South Australia, Adelaide, SA, Australia Carlos Lopez-Otin orcid.org/0000-0001-6964-1904 Departamento Bioquímica Biología Medicina, Instituto Universitario Oncología del Principado Asturias (IUOPA), Universidad Oviedo, Centro Investigación Biomédica Red Cáncer (CIBERONC), Kay F Macleod Ben May Gordon W-338, Chicago, IL, Frank Madeo Biosciences, NAWI Graz, Austria BioTechMed-Graz, Field Excellence BioHealth – Jennifer Martinez Immunity, Laboratory, Environmental NIH, Triangle Park, NC, Alicia Meléndez Department, Queens City Flushing, Graduate PhD Programs Noboru Mizushima orcid.org/0000-0002-6258-6444 Tokyo, Japan Christian Münz orcid.org/0000-0001-6419-1940 Viral Immunobiology, Experimental Zurich, Switzerland Josef Penninger Biotechnology Austrian (IMBA), Vienna BioCenter (VBC), Vienna, British Columbia, Vancouver, BC, Canada Rushika Perera orcid.org/0000-0003-2435-2273 California, San Francisco, Helen Diller Family Comprehensive Mauro Piacentini orcid.org/0000-0003-2919-1296 "Tor Vergata", Laboratory Cytology Russian Saint Petersburg, Russia Fulvio Reggiori orcid.org/0000-0003-2652-2686 Cells Systems, Section, Groningen, Netherlands C Rubinsztein Cambridge Dementia Kevin Ryan Beatson Glasgow, Junichi Sadoshima Cardiovascular Rutgers Jersey Newark, Laura Santambrogio Sandra Edward Meyer Caryl Englander Precision Luca Scorrano orcid.org/0000-0002-8515-8928 Istituto Veneto di Medicina Molecolare, Padova, Hans-Uwe Simon Pharmacology, Bern, Clinical Immunology Allergology, Sechenov Moscow, Fundamental Kazan Federal Kazan, Anna Katharina Kennedy Rheumatology, NDORMS, Oxford, Anne Simonsen orcid.org/0000-0003-4711-7057 Basic Oslo, Reprogramming, Oslo Hospital Montebello, Alexandra Stolz orcid.org/0000-0002-3340-439X Nektarios Tavernarakis orcid.org/0000-0002-5253-1466 Biotechnology, Foundation Technology-Hellas, Heraklion, Crete, Greece Sharon Tooze orcid.org/0000-0002-2182-3116 Francis Crick London, Tamotsu Yoshimori orcid.org/0000-0001-9787-3788 Osaka Suita, Intracellular Membrane Dynamics, Frontier Integrated Science Division, Open Transdisciplinary Initiatives (OTRI), Junying Yuan Interdisciplinary on Chemistry, Shanghai Organic Shanghai, Harvard Boston, Zhenyu Yue Neurology, Friedman Brain Icahn Mount Sinai, Qing Zhong orcid.org/0000-0001-6979-955X Key Differentiation Apoptosis Ministry Education, Pathophysiology, Jiao Tong (SJTU-SM), Lorenzo Galluzzi Corresponding Author [email protected] orcid.org/0000-0003-2257-8500 Dermatology, Yale Haven, CT, Pietrocola orcid.org/0000-0002-2930-234X Biosciences Nutrition, Huddinge, mor

Language: Английский

---

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 20, 2022

Abstract In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not ICIs, partly caused absence of tumor-infiltrating lymphocytes (TILs), significantly limits application ICIs. Converting these “cold” into “hot” may ICIs is an unsolved question immunotherapy. Since it a general characteristic cancers resist apoptosis, induction non-apoptotic regulated cell death (RCD) emerging as new treatment strategy. Recently, several studies have revealed interaction between RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, necroptosis exhibit synergistic responses while possibly exerting inhibitory effects on responses. Thus, targeted therapies (inducers inhibitors) against combination with exert potent activity, resistant This review summarizes multilevel relationship immunity RCD, including necroptosis, potential targeting improve efficacy malignancy.

Language: Английский

---

Autophagy-Dependent Ferroptosis: Machinery and Regulation

Cell chemical biology, Journal Year: 2020, Volume and Issue: 27(4), P. 420 - 435

Published: March 10, 2020

Language: Английский

---

Ferroptosis in infection, inflammation, and immunity

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(6)

Published: May 12, 2021

Ferroptosis is a type of regulated necrosis that triggered by combination iron toxicity, lipid peroxidation, and plasma membrane damage. The upstream inducers ferroptosis can be divided into two categories (biological versus chemical) activate major pathways (the extrinsic/transporter the intrinsic/enzymatic pathways). Excessive or deficient ferroptotic cell death implicated in growing list physiological pathophysiological processes, coupled to dysregulated immune response. This review focuses on new discoveries related how cells their spilled contents shape innate adaptive immunity health disease. Understanding immunological characteristics activity not only illuminates an intersection between but may also lead development novel treatment approaches for immunopathological diseases.

Language: Английский

---

The interaction between ferroptosis and lipid metabolism in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: June 30, 2020

Abstract Ferroptosis is a new form of programmed cell death characterized by the accumulation iron-dependent lethal lipid peroxides. Recent discoveries have focused on alterations that occur in metabolism during ferroptosis and provided intriguing insights into interplay between cancer. Their interaction regulates initiation, development, metastasis, therapy resistance cancer, as well tumor immunity, which offers several potential strategies for cancer treatment. This review brief overview features characterizing metabolism, highlights significance this

Language: Английский

---

Ferroptosis in cancer and cancer immunotherapy

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(2), P. 88 - 116

Published: Feb. 1, 2022

Abstract The hallmark of tumorigenesis is the successful circumvention cell death regulation for achieving unlimited replication and immortality. Ferroptosis a newly identified type dependent on lipid peroxidation which differs from classical programmed in terms morphology, physiology biochemistry. broad spectrum injury tumor tolerance are main reasons radiotherapy chemotherapy failure. effective rate immunotherapy as new treatment method less than 30%. can be seen radiotherapy, chemotherapy, immunotherapy; therefore, ferroptosis activation may potential strategy to overcome drug resistance mechanism traditional cancer treatments. In this review, characteristics causes by briefly described. addition, three metabolic regulations its crosstalk with signaling pathways summarized. Collectively, these findings suggest vital role based interaction immunotherapy, thus, indicating remarkable treatment.

Language: Английский

---

Oxidative Damage and Antioxidant Defense in Ferroptosis

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Sept. 17, 2020

Many new types of regulated cell death have been recently implicated in human health and disease. These deaths different morphological, genetic, biochemical, functional hallmarks. Ferroptosis was originally described as a carcinogenic RAS-dependent non-apoptotic death, is now defined type necrosis characterized by iron accumulation, lipid peroxidation, the release damage-associated molecular patterns (DAMPs). Multiple oxidative antioxidant systems, acting together autophagy machinery, shape process peroxidation during ferroptosis. In particular, production reactive oxygen species (ROS) that depends on activity NADPH oxidases (NOXs) mitochondrial respiratory chain promotes lipoxygenase (ALOX) or cytochrome P450 reductase (POR). contrast, glutathione (GSH), coenzyme Q10 (CoQ10), tetrahydrobiopterin (BH4) system limits damage processes are further transcriptionally nuclear factor, erythroid 2-like 2 (NFE2L2/NRF2), whereas membrane repair ferroptotic requires activation endosomal sorting complexes required for transport (ESCRT)-III. A understanding function ferroptosis may provide precise treatment strategies

Language: Английский

---