Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome

被引:180
|
作者
De Domenico, Ivana
Vaughn, Michael B.
Li, Liangtao
Bagley, Dustin
Musci, Giovanni
Ward, Diane M.
Kaplan, Jerry
机构
[1] Univ Utah, Dept Pathol, Sch Med, Salt Lake City, UT 84132 USA
[2] Univ Molise, Dipartimento Sci & Tecnol Agroalimentari Ambienta, Campobasso, Italy
来源
EMBO JOURNAL | 2006年 / 25卷 / 22期
关键词
ferritin; iron; proteasome; ubiquitin; yeast;
D O I
10.1038/sj.emboj.7601409
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ferritin is a cytosolic molecule comprised of subunits that self-assemble into a nanocage capable of containing up to 4500 iron atoms. Iron stored within ferritin can be mobilized for use within cells or exported from cells. Expression of ferroportin (Fpn) results in export of cytosolic iron and ferritin degradation. Fpn-mediated iron loss from ferritin occurs in the cytosol and precedes ferritin degradation by the proteasome. Depletion of ferritin iron induces the monoubiquitination of ferritin subunits. Ubiquitination is not required for iron release but is required for disassembly of ferritin nanocages, which is followed by degradation of ferritin by the proteasome. Specific mammalian machinery is not required to extract iron from ferritin. Iron can be removed from ferritin when ferritin is expressed in Saccharomyces cerevisiae, which does not have endogenous ferritin. Expressed ferritin is monoubiquitinated and degraded by the proteasome. Exposure of ubiquitination defective mammalian cells to the iron chelator desferrioxamine leads to degradation of ferritin in the lysosome, which can be prevented by inhibitors of autophagy. Thus, ferritin degradation can occur through two different mechanisms.
引用
收藏
页码:5396 / 5404
页数:9
相关论文
共 50 条
  • [41] IRON TRANSFER FROM TRANSFERRIN TO FERRITIN MEDIATED BY PYROPHOSPHATE
    KONOPKA, K
    MARESCHAL, JC
    CRICHTON, RR
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1980, 96 (03) : 1408 - 1413
  • [42] Reductive Mobilization of Iron from Intact Ferritin: Mechanisms and Physiological Implication
    Bou-Abdallah, Fadi
    Paliakkara, John J.
    Melman, Galina
    Melman, Artem
    PHARMACEUTICALS, 2018, 11 (04)
  • [43] Iron Mobilization from Ferritin in Yeast Cell Lysate and Physiological Implications
    Smith, Gideon L.
    Srivastava, Ayush K.
    Reutovich, Aliaksandra A.
    Hunter, Nathan J.
    Arosio, Paolo
    Melman, Artem
    Bou-Abdallah, Fadi
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (11)
  • [44] ROLE OF LYSOSOMES AND DMT1 IN MOBILIZATION OF FERRITIN IRON STORES
    Morgan, Jessica
    Kidane, Theodros Z.
    La, Alice
    Annie Nguyen
    Gonzalez, Angelica
    Sauble, Eric
    Linder, Maria C.
    AMERICAN JOURNAL OF HEMATOLOGY, 2013, 88 (05) : E190 - E190
  • [45] Ultrasound-mediated release of iron from ferritin
    Morrissey, JM
    Taylor, KD
    Gilman, SD
    ULTRASOUND IN MEDICINE AND BIOLOGY, 2003, 29 (12): : 1799 - 1803
  • [46] Induction of ferritin synthesis as an indicator of intracellular iron mobilization from particulates
    Fang, R
    Aust, AE
    FASEB JOURNAL, 1997, 11 (09): : A1404 - A1404
  • [47] Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions
    Fujimaki, Motoki
    Furuya, Norihiko
    Saiki, Shinji
    Amo, Taku
    Imamichi, Yoko
    Hattori, Nobutaka
    MOLECULAR AND CELLULAR BIOLOGY, 2019, 39 (14)
  • [48] Iron Acquisition in Bacillus cereus: The Roles of IlsA and Bacillibactin in Exogenous Ferritin Iron Mobilization
    Segond, Diego
    Khalil, Elise Abi
    Buisson, Christophe
    Daou, Nadine
    Kallassy, Mireille
    Lereclus, Didier
    Arosio, Paolo
    Bou-Abdallah, Fadi
    Le Roux, Christina Nielsen
    PLOS PATHOGENS, 2014, 10 (02)
  • [49] THE MOBILIZATION OF FERRITIN IRON BY LIVER CYTOSOL - A COMPARISON OF XANTHINE AND NADH AS REDUCING SUBSTRATES
    TOPHAM, R
    GOGER, M
    PEARCE, K
    SCHULTZ, P
    BIOCHEMICAL JOURNAL, 1989, 261 (01) : 137 - 143
  • [50] MECHANISMS OF GENERATION OF OXYGEN RADICALS AND REDUCTIVE MOBILIZATION OF FERRITIN IRON BY LIPOAMIDE DEHYDROGENASE
    BANDO, Y
    AKI, K
    JOURNAL OF BIOCHEMISTRY, 1991, 109 (03): : 450 - 454