Lysosomal Proteolysis Is the Primary Degradation Pathway for Cytosolic Ferritin and Cytosolic Ferritin Degradation Is Necessary for Iron Exit

	Lysosomal Proteolysis Is the Primary Degradation Pathway for Cytosolic Ferritin and Cytosolic Ferritin Degradation Is Necessary for Iron Exit
	Zhang, YH; Mikhael, M; Xu, DX; Li, YY; Shan, SL; Ning, B; Li, W; Nie, GJ; Zhao, YL; Ponka, P
刊名	ANTIOXIDANTS & REDOX SIGNALING
	2010
卷号	13 期号:7 页码:999-1009
通讯作者	[Zhang, Yinghui ; Xu, Dongxue ; Li, Yiye ; Ning, Bo ; Nie, Guangjun ; Zhao, Yuliang] Natl Ctr Nanosci & Technol China, CAS Key Lab Biol Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China ; Chinese Acad Sci, Grad Univ, Beijing, Peoples R China ; [Zhang, Yinghui] Tibet Natl Inst, Key Lab High Altitude Environm & Dis Related Gene, Dept Med, Xianyang, Shanxi, Peoples R China ; [Mikhael, Marc ; Shan Soe-Lin ; Ponka, Prem] McGill Univ, Lady Davis Inst Med Res, Sir Mortimer B Davis Jewish Gen Hosp, Montreal, PQ, Canada ; [Xu, Dongxue] Jilin Univ, Key Lab Mol Enzymol & Engn, Minist Educ, Changchun, Peoples R China ; [Li, Wei ; Zhao, Yuliang] Chinese Acad Sci, Inst High Energy Phys, Beijing, Peoples R China
英文摘要	Cytosolic ferritins sequester and store iron, consequently protecting cells against iron-mediated free radical damage. However, the mechanisms of iron exit from the ferritin cage and reutilization are largely unknown. In a previous study, we found that mitochondrial ferritin (MtFt) expression led to a decrease in cytosolic ferritin. Here we showed that treatment with inhibitors of lysosomal proteases largely blocked cytosolic ferritin loss in both MtFt-expressing and wild-type cells. Moreover, cytosolic ferritin in cells treated with inhibitors of lysosomal proteases was found to store more iron than did cytosolic ferritins in untreated cells. The prevention of cytosolic ferritin degradation in MtFt-expressing cells significantly blocked iron mobilization from the protein cage induced by MtFt expression. These studies also showed that blockage of cytosolic ferritin loss by leupeptin resulted in decreased cytosolic ferritin synthesis and prolonged cytosolic ferritin stability, potentially resulting in diminished iron availability. Lastly, we found that proteasomes were responsible for cytosolic ferritin degradation in cells pretreated with ferric ammonium citrate. Thus, the current studies suggest that cytosolic ferritin degradation precedes the release of iron in MtFt-expressing cells; that MtFt-induced cytosolic ferritin decrease is partially preventable by lysosomal protease inhibitors; and that both lysosomal and proteasomal pathways may be involved in cytosolic ferritin degradation. Antioxid. Redox Signal. 13, 999-1009.
学科主题	Biochemistry & Molecular Biology; Endocrinology & Metabolism
类目[WOS]	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
研究领域[WOS]	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
原文出处	SCI
语种	英语
WOS记录号	WOS:000281100300005
内容类型	期刊论文
源URL	[http://ir.ihep.ac.cn/handle/311005/238874]
专题	高能物理研究所_多学科研究中心
作者单位	中国科学院高能物理研究所
推荐引用方式 GB/T 7714	Zhang, YH,Mikhael, M,Xu, DX,et al. Lysosomal Proteolysis Is the Primary Degradation Pathway for Cytosolic Ferritin and Cytosolic Ferritin Degradation Is Necessary for Iron Exit[J]. ANTIOXIDANTS & REDOX SIGNALING,2010,13(7):999-1009.
APA	Zhang, YH.,Mikhael, M.,Xu, DX.,Li, YY.,Shan, SL.,...&赵宇亮.(2010).Lysosomal Proteolysis Is the Primary Degradation Pathway for Cytosolic Ferritin and Cytosolic Ferritin Degradation Is Necessary for Iron Exit.ANTIOXIDANTS & REDOX SIGNALING,13(7),999-1009.
MLA	Zhang, YH,et al."Lysosomal Proteolysis Is the Primary Degradation Pathway for Cytosolic Ferritin and Cytosolic Ferritin Degradation Is Necessary for Iron Exit".ANTIOXIDANTS & REDOX SIGNALING 13.7(2010):999-1009.