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

被引:181
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
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 39 条
  • [21] CCC1 is a transporter that mediates vacuolar iron storage in yeast
    Li, LT
    Chen, OS
    Ward, DM
    Kaplan, J
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (31) : 29515 - 29519
  • [22] Ferritins: Dynamic management of biological iron and oxygen chemistry
    Liu, XF
    Theil, EC
    [J]. ACCOUNTS OF CHEMICAL RESEARCH, 2005, 38 (03) : 167 - 175
  • [23] A FancD2-monoubiquitin fusion reveals hidden functions of Fanconi anemia core complex in DNA repair
    Matsushita, N
    Kitao, H
    Ishiai, M
    Nagashima, N
    Hirano, S
    Okawa, K
    Ohta, T
    Yu, DS
    McHugh, PJ
    Hickson, ID
    Venkitaraman, AR
    Kurumizaka, H
    Takata, M
    [J]. MOLECULAR CELL, 2005, 19 (06) : 841 - 847
  • [24] Oxidation-induced ferritin turnover in microglial cells: role of proteasome
    Mehlhase, J
    Sandig, G
    Pantopoulos, K
    Grune, T
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2005, 38 (02) : 276 - 285
  • [25] MERTZ JR, 1983, J BIOL CHEM, V258, P1719
  • [26] Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization
    Nemeth, E
    Tuttle, MS
    Powelson, J
    Vaughn, MB
    Donovan, A
    Ward, DM
    Ganz, T
    Kaplan, J
    [J]. SCIENCE, 2004, 306 (5704) : 2090 - 2093
  • [27] Nutrient deprivation of cultured rat hepatocytes increases the desferrioxamine-available iron pool and augments the sensitivity to hydrogen peroxide
    Ollinger, K
    Roberg, K
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (38) : 23707 - 23711
  • [28] IRON-METABOLISM IN MURINE ERYTHROLEUKAEMIC CELLS
    PETO, TEA
    RUTHERFORD, TR
    THOMPSON, JL
    WEATHERALL, DJ
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 1983, 54 (04) : 623 - 631
  • [29] Deferoxamine pharmacokinetics
    Porter, JB
    [J]. SEMINARS IN HEMATOLOGY, 2001, 38 (01) : 63 - 68
  • [30] Iron in cytosolic ferritin can be recycled through lysosomal degradation in human fibroblasts
    Radisky, DC
    Kaplan, J
    [J]. BIOCHEMICAL JOURNAL, 1998, 336 : 201 - 205