TY - JOUR
T1 - Ferroptosis
T2 - A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
AU - Stockwell, Brent R.
AU - Friedmann Angeli, José Pedro
AU - Bayir, Hülya
AU - Bush, Ashley I.
AU - Conrad, Marcus
AU - Dixon, Scott J.
AU - Fulda, Simone
AU - Gascón, Sergio
AU - Hatzios, Stavroula K.
AU - Kagan, Valerian E.
AU - Noel, Kay
AU - Jiang, Xuejun
AU - Linkermann, Andreas
AU - Murphy, Maureen E.
AU - Overholtzer, Michael
AU - Oyagi, Atsushi
AU - Pagnussat, Gabriela C.
AU - Park, Jason
AU - Ran, Qitao
AU - Rosenfeld, Craig S.
AU - Salnikow, Konstantin
AU - Tang, Daolin
AU - Torti, Frank M.
AU - Torti, Suzy V.
AU - Toyokuni, Shinya
AU - Woerpel, K. A.
AU - Zhang, Donna D.
N1 - Funding Information:
We thank The Banbury Center at Cold Spring Harbor Labs for hosting a meeting of the authors that served as the genesis of this manuscript. We thank the following funding organizations: NIH ( R35CA209896 and P01 CA087497 to B.R.S.; 4R00CA166517 and 1R01GM122923 to S.J.D.; R01CA171101 to F.M.T.; R01CA188025 to S.V.T.; CA102184 to M.E.M.; HL114453 , U19AI068021 , NS076511 , and NS061817 to V.E.K. and H.B.; R01GM115366 and 1R01GM118730 to K.A.W.; R01CA204232 and P30CA008748 to X.J.; and R01CA160417 to D.T.), JSPS KAKENHI ( JP16K15257 and JP17H04064 to S.V.T.), ACS ( RSG-16-014-01-CDD to D.T.), NNSFC ( 2016A030308011 and 31671435 to D.T.), Geoffrey Beene Cancer Research Center grant to X.J., and HFSP ( RGP 0013/14 to M.C. and V.E.K.). C.S.R. is an employee of and has a profit interest in Collaborative Medicinal Development. K.N. is a paid consultant of and has a profit interest in Collaborative Medicinal Development. A.I.B. is a shareholder in Prana Biotechnology, Mesoblast, Grunbiotics Pty, and Cogstate and is a paid consultant for and has a profit interest in Collaborative Medicinal Development.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/10/5
Y1 - 2017/10/5
N2 - Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death. Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.
AB - Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death. Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.
KW - PUFA
KW - ROS
KW - cancer
KW - cell death
KW - ferroptosis
KW - glutathione
KW - iron
KW - metabolism
KW - neurodegeneration
KW - peroxidation
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U2 - 10.1016/j.cell.2017.09.021
DO - 10.1016/j.cell.2017.09.021
M3 - Review article
C2 - 28985560
AN - SCOPUS:85030552365
SN - 0092-8674
VL - 171
SP - 273
EP - 285
JO - Cell
JF - Cell
IS - 2
ER -