Identification of Frataxin as a regulator of ferroptosis.
Identifieur interne : 000109 ( Main/Exploration ); précédent : 000108; suivant : 000110Identification of Frataxin as a regulator of ferroptosis.
Auteurs : Jing Du [République populaire de Chine] ; Yi Zhou [République populaire de Chine] ; Yanchun Li [République populaire de Chine] ; Jun Xia [République populaire de Chine] ; Yongjian Chen [République populaire de Chine] ; Sufeng Chen [République populaire de Chine] ; Xin Wang [République populaire de Chine] ; Weidong Sun [République populaire de Chine] ; Tongtong Wang [République populaire de Chine] ; Xueying Ren [République populaire de Chine] ; Xu Wang [République populaire de Chine] ; Yihan An [République populaire de Chine] ; Kang Lu [République populaire de Chine] ; Wanye Hu [République populaire de Chine] ; Siyuan Huang [République populaire de Chine] ; Jianghui Li [République populaire de Chine] ; Xiangmin Tong [République populaire de Chine] ; Ying Wang [République populaire de Chine]Source :
- Redox biology [ 2213-2317 ] ; 2020.
Abstract
Ferroptosis is a newly discovered form of non-apoptotic regulated cell death and is characterized by iron-dependent and lipid peroxidation. Due to the enhanced dependence on iron in cancer cells, induction of ferroptosis is becoming a promising therapeutic strategy. However, the precise underlying molecular mechanism and regulation process of ferroptosis remains largely unknown. In the present study, we demonstrate that the protein Frataxin (FXN) is a key regulator of ferroptosis by modulating iron homeostasis and mitochondrial function. Suppression of FXN expression specifically repressed the proliferation, destroyed mitochondrial morphology, impeded Fe-S cluster assembly and activated iron starvation stress. Moreover, suppression of FXN expression significantly enhanced erastin-induced cell death through accelerating free iron accumulation, lipid peroxidation and resulted in dramatic mitochondria morphological damage including enhanced fragmentation and vanished cristae. In addition, this type of cell death was confirmed to be ferroptosis, since it could be pharmacologically restored by ferroptotic inhibitor Fer-1 or GSH, but not by inhibitors of apoptosis, necrosis. Vice versa, enforced expression of FXN blocked iron starvation response and erastin-induced ferroptosis. More importantly, pharmacological or genetic blocking the signal of iron starvation could completely restore the resistance to ferroptosis in FXN knockdown cells and xenograft graft in vivo. This paper suggests that FXN is a novel ferroptosis modulator, as well as a potential provided target to improve the antitumor activity based on ferroptosis.
DOI: 10.1016/j.redox.2020.101483
PubMed: 32169822
PubMed Central: PMC7068686
Affiliations:
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Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yanchun" sort="Li, Yanchun" uniqKey="Li Y" first="Yanchun" last="Li">Yanchun Li</name><affiliation wicri:level="1"><nlm:affiliation>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053</wicri:regionArea><wicri:noRegion>310053</wicri:noRegion></affiliation></author><author><name sortKey="Xia, Jun" sort="Xia, Jun" uniqKey="Xia J" first="Jun" last="Xia">Jun Xia</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yongjian" sort="Chen, Yongjian" uniqKey="Chen Y" first="Yongjian" last="Chen">Yongjian Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Sufeng" sort="Chen, Sufeng" uniqKey="Chen S" first="Sufeng" last="Chen">Sufeng Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Weidong" sort="Sun, Weidong" uniqKey="Sun W" first="Weidong" last="Sun">Weidong Sun</name><affiliation wicri:level="1"><nlm:affiliation>Department of Hematology, Shaoxing Central Hospital, Shaoxing, Zhejiang, 312030, China; Bengbu Medical College, Bengbu, Anhui, 233000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, Shaoxing Central Hospital, Shaoxing, Zhejiang, 312030, China; Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Tongtong" sort="Wang, Tongtong" uniqKey="Wang T" first="Tongtong" last="Wang">Tongtong Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Ren, Xueying" sort="Ren, Xueying" uniqKey="Ren X" first="Xueying" last="Ren">Xueying Ren</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Xu" sort="Wang, Xu" uniqKey="Wang X" first="Xu" last="Wang">Xu Wang</name><affiliation wicri:level="1"><nlm:affiliation>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035</wicri:regionArea><wicri:noRegion>325035</wicri:noRegion></affiliation></author><author><name sortKey="An, Yihan" sort="An, Yihan" uniqKey="An Y" first="Yihan" last="An">Yihan An</name><affiliation wicri:level="1"><nlm:affiliation>Bengbu Medical College, Bengbu, Anhui, 233000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Kang" sort="Lu, Kang" uniqKey="Lu K" first="Kang" last="Lu">Kang Lu</name><affiliation wicri:level="1"><nlm:affiliation>Bengbu Medical College, Bengbu, Anhui, 233000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Wanye" sort="Hu, Wanye" uniqKey="Hu W" first="Wanye" last="Hu">Wanye Hu</name><affiliation wicri:level="1"><nlm:affiliation>Bengbu Medical College, Bengbu, Anhui, 233000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Siyuan" sort="Huang, Siyuan" uniqKey="Huang S" first="Siyuan" last="Huang">Siyuan Huang</name><affiliation wicri:level="1"><nlm:affiliation>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053</wicri:regionArea><wicri:noRegion>310053</wicri:noRegion></affiliation></author><author><name sortKey="Li, Jianghui" sort="Li, Jianghui" uniqKey="Li J" first="Jianghui" last="Li">Jianghui Li</name><affiliation wicri:level="1"><nlm:affiliation>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035</wicri:regionArea><wicri:noRegion>325035</wicri:noRegion></affiliation></author><author><name sortKey="Tong, Xiangmin" sort="Tong, Xiangmin" uniqKey="Tong X" first="Xiangmin" last="Tong">Xiangmin Tong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Bengbu Medical College, Bengbu, Anhui, 233000, China. Electronic address: tongxiangming@hmc.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><affiliation wicri:level="1"><nlm:affiliation>Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Bengbu Medical College, Bengbu, Anhui, 233000, China. Electronic address: wangying@hmc.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32169822</idno><idno type="pmid">32169822</idno><idno type="doi">10.1016/j.redox.2020.101483</idno><idno type="pmc">PMC7068686</idno><idno type="wicri:Area/Main/Corpus">000127</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000127</idno><idno type="wicri:Area/Main/Curation">000127</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000127</idno><idno type="wicri:Area/Main/Exploration">000127</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Identification of Frataxin as a regulator of ferroptosis.</title><author><name sortKey="Du, Jing" sort="Du, Jing" uniqKey="Du J" first="Jing" last="Du">Jing Du</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Yi" sort="Zhou, Yi" uniqKey="Zhou Y" first="Yi" last="Zhou">Yi Zhou</name><affiliation wicri:level="1"><nlm:affiliation>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yanchun" sort="Li, Yanchun" uniqKey="Li Y" first="Yanchun" last="Li">Yanchun Li</name><affiliation wicri:level="1"><nlm:affiliation>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053</wicri:regionArea><wicri:noRegion>310053</wicri:noRegion></affiliation></author><author><name sortKey="Xia, Jun" sort="Xia, Jun" uniqKey="Xia J" first="Jun" last="Xia">Jun Xia</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yongjian" sort="Chen, Yongjian" uniqKey="Chen Y" first="Yongjian" last="Chen">Yongjian Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Sufeng" sort="Chen, Sufeng" uniqKey="Chen S" first="Sufeng" last="Chen">Sufeng Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Weidong" sort="Sun, Weidong" uniqKey="Sun W" first="Weidong" last="Sun">Weidong Sun</name><affiliation wicri:level="1"><nlm:affiliation>Department of Hematology, Shaoxing Central Hospital, Shaoxing, Zhejiang, 312030, China; Bengbu Medical College, Bengbu, Anhui, 233000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Hematology, Shaoxing Central Hospital, Shaoxing, Zhejiang, 312030, China; Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Tongtong" sort="Wang, Tongtong" uniqKey="Wang T" first="Tongtong" last="Wang">Tongtong Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Ren, Xueying" sort="Ren, Xueying" uniqKey="Ren X" first="Xueying" last="Ren">Xueying Ren</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014</wicri:regionArea><wicri:noRegion>310014</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Xu" sort="Wang, Xu" uniqKey="Wang X" first="Xu" last="Wang">Xu Wang</name><affiliation wicri:level="1"><nlm:affiliation>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035</wicri:regionArea><wicri:noRegion>325035</wicri:noRegion></affiliation></author><author><name sortKey="An, Yihan" sort="An, Yihan" uniqKey="An Y" first="Yihan" last="An">Yihan An</name><affiliation wicri:level="1"><nlm:affiliation>Bengbu Medical College, Bengbu, Anhui, 233000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Kang" sort="Lu, Kang" uniqKey="Lu K" first="Kang" last="Lu">Kang Lu</name><affiliation wicri:level="1"><nlm:affiliation>Bengbu Medical College, Bengbu, Anhui, 233000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Wanye" sort="Hu, Wanye" uniqKey="Hu W" first="Wanye" last="Hu">Wanye Hu</name><affiliation wicri:level="1"><nlm:affiliation>Bengbu Medical College, Bengbu, Anhui, 233000, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Siyuan" sort="Huang, Siyuan" uniqKey="Huang S" first="Siyuan" last="Huang">Siyuan Huang</name><affiliation wicri:level="1"><nlm:affiliation>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053</wicri:regionArea><wicri:noRegion>310053</wicri:noRegion></affiliation></author><author><name sortKey="Li, Jianghui" sort="Li, Jianghui" uniqKey="Li J" first="Jianghui" last="Li">Jianghui Li</name><affiliation wicri:level="1"><nlm:affiliation>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035</wicri:regionArea><wicri:noRegion>325035</wicri:noRegion></affiliation></author><author><name sortKey="Tong, Xiangmin" sort="Tong, Xiangmin" uniqKey="Tong X" first="Xiangmin" last="Tong">Xiangmin Tong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Bengbu Medical College, Bengbu, Anhui, 233000, China. Electronic address: tongxiangming@hmc.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><affiliation wicri:level="1"><nlm:affiliation>Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Bengbu Medical College, Bengbu, Anhui, 233000, China. Electronic address: wangying@hmc.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Bengbu Medical College, Bengbu, Anhui, 233000</wicri:regionArea><wicri:noRegion>233000</wicri:noRegion></affiliation></author></analytic><series><title level="j">Redox biology</title><idno type="eISSN">2213-2317</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Ferroptosis is a newly discovered form of non-apoptotic regulated cell death and is characterized by iron-dependent and lipid peroxidation. Due to the enhanced dependence on iron in cancer cells, induction of ferroptosis is becoming a promising therapeutic strategy. However, the precise underlying molecular mechanism and regulation process of ferroptosis remains largely unknown. In the present study, we demonstrate that the protein Frataxin (FXN) is a key regulator of ferroptosis by modulating iron homeostasis and mitochondrial function. Suppression of FXN expression specifically repressed the proliferation, destroyed mitochondrial morphology, impeded Fe-S cluster assembly and activated iron starvation stress. Moreover, suppression of FXN expression significantly enhanced erastin-induced cell death through accelerating free iron accumulation, lipid peroxidation and resulted in dramatic mitochondria morphological damage including enhanced fragmentation and vanished cristae. In addition, this type of cell death was confirmed to be ferroptosis, since it could be pharmacologically restored by ferroptotic inhibitor Fer-1 or GSH, but not by inhibitors of apoptosis, necrosis. Vice versa, enforced expression of FXN blocked iron starvation response and erastin-induced ferroptosis. More importantly, pharmacological or genetic blocking the signal of iron starvation could completely restore the resistance to ferroptosis in FXN knockdown cells and xenograft graft in vivo. This paper suggests that FXN is a novel ferroptosis modulator, as well as a potential provided target to improve the antitumor activity based on ferroptosis.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32169822</PMID><DateRevised><Year>2020</Year><Month>06</Month><Day>26</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2213-2317</ISSN><JournalIssue CitedMedium="Internet"><Volume>32</Volume><PubDate><Year>2020</Year><Month>05</Month></PubDate></JournalIssue><Title>Redox biology</Title><ISOAbbreviation>Redox Biol</ISOAbbreviation></Journal><ArticleTitle>Identification of Frataxin as a regulator of ferroptosis.</ArticleTitle><Pagination><MedlinePgn>101483</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S2213-2317(19)31475-2</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.redox.2020.101483</ELocationID><Abstract><AbstractText>Ferroptosis is a newly discovered form of non-apoptotic regulated cell death and is characterized by iron-dependent and lipid peroxidation. Due to the enhanced dependence on iron in cancer cells, induction of ferroptosis is becoming a promising therapeutic strategy. However, the precise underlying molecular mechanism and regulation process of ferroptosis remains largely unknown. In the present study, we demonstrate that the protein Frataxin (FXN) is a key regulator of ferroptosis by modulating iron homeostasis and mitochondrial function. Suppression of FXN expression specifically repressed the proliferation, destroyed mitochondrial morphology, impeded Fe-S cluster assembly and activated iron starvation stress. Moreover, suppression of FXN expression significantly enhanced erastin-induced cell death through accelerating free iron accumulation, lipid peroxidation and resulted in dramatic mitochondria morphological damage including enhanced fragmentation and vanished cristae. In addition, this type of cell death was confirmed to be ferroptosis, since it could be pharmacologically restored by ferroptotic inhibitor Fer-1 or GSH, but not by inhibitors of apoptosis, necrosis. Vice versa, enforced expression of FXN blocked iron starvation response and erastin-induced ferroptosis. More importantly, pharmacological or genetic blocking the signal of iron starvation could completely restore the resistance to ferroptosis in FXN knockdown cells and xenograft graft in vivo. This paper suggests that FXN is a novel ferroptosis modulator, as well as a potential provided target to improve the antitumor activity based on ferroptosis.</AbstractText><CopyrightInformation>Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Du</LastName><ForeName>Jing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Yi</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yanchun</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xia</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Yongjian</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Sufeng</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Xin</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Weidong</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Hematology, Shaoxing Central Hospital, Shaoxing, Zhejiang, 312030, China; Bengbu Medical College, Bengbu, Anhui, 233000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Tongtong</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Wangjiangshan, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ren</LastName><ForeName>Xueying</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Xu</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>An</LastName><ForeName>Yihan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Bengbu Medical College, Bengbu, Anhui, 233000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Kang</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Bengbu Medical College, Bengbu, Anhui, 233000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>Wanye</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Bengbu Medical College, Bengbu, Anhui, 233000, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Siyuan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jianghui</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tong</LastName><ForeName>Xiangmin</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Bengbu Medical College, Bengbu, Anhui, 233000, China. Electronic address: tongxiangming@hmc.edu.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Bengbu Medical College, Bengbu, Anhui, 233000, China. Electronic address: wangying@hmc.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>03</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Redox Biol</MedlineTA><NlmUniqueID>101605639</NlmUniqueID><ISSNLinking>2213-2317</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Ferroptosis</Keyword><Keyword MajorTopicYN="Y">Frataxin</Keyword><Keyword MajorTopicYN="Y">Iron-sulfur cluster</Keyword><Keyword MajorTopicYN="Y">Mitochondria</Keyword></KeywordList><CoiStatement>Declaration of competing interest The authors declare that there is no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>11</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>02</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>02</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>3</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>3</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>3</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32169822</ArticleId><ArticleId IdType="pii">S2213-2317(19)31475-2</ArticleId><ArticleId IdType="doi">10.1016/j.redox.2020.101483</ArticleId><ArticleId IdType="pmc">PMC7068686</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Du, Jing" sort="Du, Jing" uniqKey="Du J" first="Jing" last="Du">Jing Du</name></noRegion><name sortKey="An, Yihan" sort="An, Yihan" uniqKey="An Y" first="Yihan" last="An">Yihan An</name><name sortKey="Chen, Sufeng" sort="Chen, Sufeng" uniqKey="Chen S" first="Sufeng" last="Chen">Sufeng Chen</name><name sortKey="Chen, Yongjian" sort="Chen, Yongjian" uniqKey="Chen Y" first="Yongjian" last="Chen">Yongjian Chen</name><name sortKey="Hu, Wanye" sort="Hu, Wanye" uniqKey="Hu W" first="Wanye" last="Hu">Wanye Hu</name><name sortKey="Huang, Siyuan" sort="Huang, Siyuan" uniqKey="Huang S" first="Siyuan" last="Huang">Siyuan Huang</name><name sortKey="Li, Jianghui" sort="Li, Jianghui" uniqKey="Li J" first="Jianghui" last="Li">Jianghui Li</name><name sortKey="Li, Yanchun" sort="Li, Yanchun" uniqKey="Li Y" first="Yanchun" last="Li">Yanchun Li</name><name sortKey="Lu, Kang" sort="Lu, Kang" uniqKey="Lu K" first="Kang" last="Lu">Kang Lu</name><name sortKey="Ren, Xueying" sort="Ren, Xueying" uniqKey="Ren X" first="Xueying" last="Ren">Xueying Ren</name><name sortKey="Sun, Weidong" sort="Sun, Weidong" uniqKey="Sun W" first="Weidong" last="Sun">Weidong Sun</name><name sortKey="Tong, Xiangmin" sort="Tong, Xiangmin" uniqKey="Tong X" first="Xiangmin" last="Tong">Xiangmin Tong</name><name sortKey="Wang, Tongtong" sort="Wang, Tongtong" uniqKey="Wang T" first="Tongtong" last="Wang">Tongtong Wang</name><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><name sortKey="Wang, Xu" sort="Wang, Xu" uniqKey="Wang X" first="Xu" last="Wang">Xu Wang</name><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><name sortKey="Xia, Jun" sort="Xia, Jun" uniqKey="Xia J" first="Jun" last="Xia">Jun Xia</name><name sortKey="Zhou, Yi" sort="Zhou, Yi" uniqKey="Zhou Y" first="Yi" last="Zhou">Yi Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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