Double-edged Sword Role of Iron-loaded Ferritin in Extracellular Vesicles

Shinya Toyokuni; Yingyi Kong; Hao Zheng; Danyang Mi; Misako Katabuchi; Yashiro Motooka; Fumiya Ito

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자료유형: 학술저널

저자정보: Shinya Toyokuni (Nagoya University) Yingyi Kong (Nagoya University) Hao Zheng (Nagoya University) Danyang Mi (Nagoya University) Misako Katabuchi (Nagoya University) Yashiro Motooka (Nagoya University) Fumiya Ito (Nagoya University)

저널정보: 대한암예방학회 대한암예방학회지 대한암예방학회지 제26권 제4호

발행연도: 2021.12

수록면: 244 - 249 (6page)

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Human epidemiological and animal studies have demonstrated that excess iron is a risk for cancer. The responsible mechanisms are: 1) increased intracellular iron catalyzes the Fenton reaction to generate hydroxyl radicals, leading to mutagenic oxidative DNA lesions; 2) iron is necessary for cellular proliferation as cofactors of many enzymes. Thus, iron-excess milieu promotes selecting cellular evolution to ferroptosis-resistance, a major basis for carcinogenesis. Ferritin is a 24-subunit nanocage protein required for iron storage under the regulation of the iron-regulatory protein (IRP)/iron-responsive element (IRE) system. Ferritin is a serum marker, representing total body iron storage. However, how ferritin is secreted extracellularly has been unelucidated. We recently discovered that an exosomal marker CD63 is regulated by the IRP/IRE system and that iron-loaded ferritin is secreted as extracel lular vesicles under the guidance of nuclear receptor coactivator 4 (NCOA4). On the other hand, we found that macrophages under asbestos-induced ferroptosis emit ferroptosis-dependent extracellular vesicles (FedEVs), which are received by nearby mesothelial cells, resulting in significant mutagenic DNA damage. Therefore, cells, including macrophages, can share excess iron with other cells, via iron-loaded ferritin packaged in extracellular vesicles as safe non-catalytic iron. However, similar process, such as one involving FedEVs, may cause accumulation of excess iron in other specific cells, which may eventually promote carcinogenesis. Key Words Ferritin, Extracellular vesicles, Iron, Ferroptosis, Asbestos

#Ferritin #Extracellular vesicles #Iron #Ferroptosis #Asbestos

참고문헌 (58)

참고문헌 신청

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