Dietary Induction and Modulation of Ferroptosis in Caenorhabditis elegans
TLDR
It is demonstrated that DGLA-induced germ cell death in C. elegans is modulated by small molecule ferroptosis inhibitors, genetic manipulation of ferritin, NADPH oxidase, and glutathione peroxidases, and by dietary co-supplementation with oleic acid.Abstract:
SUMMARY Ferroptosis is an iron-dependent form of regulated cell death associated with oxidized polyunsaturated phospholipids. Understanding the role of this process in vivo has been slowed by the lack of readily accessible model systems. Exposing the nematode Caenorhabditis elegans to the polyunsaturated fatty acid dihomogamma-linolenic acid (DGLA; 20:3n-6) causes germ cell death and sterility that is largely independent of the canonical apoptosis pathway. Here we demonstrate that DGLA-induced germ cell death is modulated by small molecule ferroptosis inhibitors, genetic manipulation of ferritin, NADPH oxidase, and glutathione peroxidases, and by dietary co-supplementation with oleic acid. Thus, DGLA-induced germ cell death in C. elegans is highly analogous to ferroptosis in mammalian cells. DGLA can also induce ferroptosis in human cells, further highlighting this omega-6 PUFA as a metabolic instigator of ferroptosis. Together, these results establish C. elegans as a powerful animal model to study the induction and modulation of ferroptosis by dietary fats. Highlights - Dietary dihomogamma-linolenic acid (DGLA)-induced germ cell death in C. elegans is alleviated by small molecule antioxidants and iron chelators - Dietary and endogenous oleic acid protects from DGLA-induced ferroptosis - Ether-lipid deficiency increases sensitivity to DGLA-induced ferroptosis - DGLA specifically induces ferroptosis in human cancer cellsread more
Citations
More filters
Journal ArticleDOI
Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications.
Tianai Sun,Jen-Tsan Chi +1 more
TL;DR: YAP/TAZ and Hippo pathways are established as novel determinants of ferroptosis and inducing ferroPTosis may have therapeutic potential for YAP/ TAZ-activated chemo-resistant and metastatic tumor cells.
References
More filters
Journal ArticleDOI
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Scott J. Dixon,Kathryn M. Lemberg,Michael R. Lamprecht,Rachid Skouta,Eleina M. Zaitsev,Caroline E Gleason,Darpan N Patel,Andras J. Bauer,Alexandra M. Cantley,Wan Seok Yang,Barclay Morrison,Brent R. Stockwell,Brent R. Stockwell +12 more
TL;DR: This paper identified the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes.
Journal ArticleDOI
Systematic functional analysis of the Caenorhabditis elegans genome using RNAi
Ravi S. Kamath,Andrew G. Fraser,Andrew G. Fraser,Yan Dong,Gino B. Poulin,Richard Durbin,Monica Gotta,Alexander Kanapin,Nathalie Le Bot,Sergio Moreno,Sergio Moreno,Marc Sohrmann,David P. Welchman,Peder Zipperlen,Julie Ahringer +14 more
TL;DR: It is found that genes of similar functions are clustered in distinct, multi-megabase regions of individual chromosomes; genes in these regions tend to share transcriptional profiles.
Journal ArticleDOI
Regulation of Ferroptotic Cancer Cell Death by GPX4
Wan Seok Yang,Rohitha SriRamaratnam,Matthew Welsch,Kenichi Shimada,Rachid Skouta,Vasanthi S. Viswanathan,Vasanthi S. Viswanathan,Jaime H. Cheah,Paul A. Clemons,Alykhan F. Shamji,Clary B. Clish,Lewis M. Brown,Albert W. Girotti,Virginia W. Cornish,Stuart L. Schreiber,Brent R. Stockwell +15 more
TL;DR: Targeted metabolomic profiling and chemoproteomics revealed that GPX4 is an essential regulator of ferroptotic cancer cell death and sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPx4-regulated ferroPTosis.
Journal ArticleDOI
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Brent R. Stockwell,José Pedro Friedmann Angeli,Hülya Bayır,Ashley I. Bush,Marcus Conrad,Scott J. Dixon,Simone Fulda,Susan Gascon,Stavroula K. Hatzios,Valerian E. Kagan,Kay Noel,Xuejun Jiang,Andreas Linkermann,Maureen E. Murphy,Michael Overholtzer,Atsushi Oyagi,Gabriela Carolina Pagnussat,Jason Park,Qitao Ran,Craig S. Rosenfeld,Konstantin Salnikow,Daolin Tang,Daolin Tang,Frank M. Torti,Suzy V. Torti,Shinya Toyokuni,K. A. Woerpel,Donna D. Zhang +27 more
TL;DR: The mechanisms underlying ferroptosis are reviewed, connections to other areas of biology and medicine are highlighted, and tools and guidelines for studying this emerging form of regulated cell death are recommended.
Journal ArticleDOI
Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
José Pedro Friedmann Angeli,Manuela Schneider,Bettina Proneth,Yulia Y. Tyurina,Vladimir A. Tyurin,Victoria Jayne Hammond,Nadja Herbach,Michaela Aichler,Axel Walch,E. Eggenhofer,Devaraj Basavarajappa,Olof Rådmark,Sho Kobayashi,Tobias Seibt,Heike Beck,Frauke Neff,Irene Esposito,Rüdiger Wanke,Heidi Förster,Olena Yefremova,Marc Heinrichmeyer,Georg W. Bornkamm,Edward K. Geissler,Stephen B. Thomas,Brent R. Stockwell,Valerie B. O'Donnell,Valerian E. Kagan,Joel A. Schick,Marcus Conrad +28 more
TL;DR: It is demonstrated that ferroptosis is a pervasive and dynamic form of cell death, which, when impeded, promises substantial cytoprotection.
Related Papers (5)
Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer.
Ji Yoon Lee,Ji Yoon Lee,Miso Nam,Hye Young Son,Kwangbeom Hyun,Seo Young Jang,Jong Woo Kim,Min Wook Kim,Youngae Jung,Eunji Jang,Seon Jin Yoon,Jung-Eun Kim,Jihye Kim,Jin-Ho Seo,Jeong Ki Min,Kyoung Jin Oh,Baek Soo Han,Won Kon Kim,Kwang-Hee Bae,Kwang-Hee Bae,Jaewhan Song,Jae-Hoon Kim,Yong Min Huh,Geum-Sook Hwang,Eun-Woo Lee,Sang Chul Lee +25 more