De Domenico Ivana, Vaughn Michael B, Li Liangtao, Bagley Dustin, Musci Giovanni, Ward Diane M, Kaplan Jerry
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132, USA.
EMBO J. 2006 Nov 15;25(22):5396-404. doi: 10.1038/sj.emboj.7601409. Epub 2006 Nov 2.
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.
铁蛋白是一种胞质分子，由亚基组成，这些亚基自组装成一个能够容纳多达4500个铁原子的纳米笼。储存在铁蛋白中的铁可以被动员用于细胞内或从细胞中输出。铁转运蛋白（Fpn）的表达导致胞质铁输出和铁蛋白降解。Fpn介导的铁蛋白中铁的丢失发生在胞质溶胶中，且先于蛋白酶体介导的铁蛋白降解。铁蛋白铁的耗尽诱导铁蛋白亚基的单泛素化。泛素化对于铁的释放不是必需的，但对于铁蛋白纳米笼的拆解是必需的，随后铁蛋白被蛋白酶体降解。从铁蛋白中提取铁不需要特定的哺乳动物机制。当铁蛋白在没有内源性铁蛋白的酿酒酵母中表达时，铁可以从铁蛋白中被去除。表达的铁蛋白被单泛素化并被蛋白酶体降解。将泛素化缺陷的哺乳动物细胞暴露于铁螯合剂去铁胺会导致铁蛋白在溶酶体中降解，这可以被自噬抑制剂阻止。因此，铁蛋白降解可以通过两种不同的机制发生。
