New iron export pathways acting via holo-ferritin secretion.

Autor: Yanatori I; Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan. Electronic address: yanatori@mcp.med.kyoto-u.ac.jp., Kishi F; Kenjinkai Healthcare Corporation, Yamaguchi, 757-0001, Japan., Toyokuni S; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-ku, Nagoya, 466-8550, Japan; Center for Low-temperature Plasma Sciences, Nagoya University, Furo-Cho, Chikusa-ku, Nagoya, 464-8603, Japan.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2023 Sep 15; Vol. 746, pp. 109737. Date of Electronic Publication: 2023 Sep 07.
DOI: 10.1016/j.abb.2023.109737
Abstrakt: Ferritin is a spherical nanocage protein for iron storage, composed of 24 light- or heavy-polypeptide chain subunits. A single ferritin molecule can carry up to 4500 iron atoms in its core, which plays an important role in suppressing intracellular iron toxicity. Serum ferritin levels are used as a marker for the total amount of iron stored in the body. Most serum ferritin is iron-free (apo-ferritin) and it is unclear how ferritin is released from cells. Ferritin is secreted into serum via extracellular vesicles (EVs) or the secretory autophagy pathway but not via the classical endoplasmic reticulum (ER)-to-Golgi secretion pathway. We recently discovered that the level of tetraspanin CD63, a common EV marker, is post-transcriptionally regulated by the intracellular iron level and both CD63 and ferritin expression is induced by iron loading. Ferritin is incorporated into CD63(+)-EVs through the ferritin-specific autophagy adapter molecule, NCOA4, and then secreted from cells. EV production differs drastically depending on cell type and physiological conditions. Extracellular matrix detached cells express pentaspanin prominin 2 and prominin 2(+)-EVs secrete ferritin independently of NCOA4 trafficking. Ferritin is tightly bound to iron in EVs and functions as an iron-carrier protein in the extracellular environment. Cells can suppress ferroptosis by secreting holo-ferritin, which reduces intracellular iron concentration. However, this exposes the neighboring cells receiving the secreted holo-ferritin to a large excess of iron. This results in cellular toxicity through increased generation of reactive oxygen species (ROS). Here we review the machinery by which ferritin is incorporated into EVs and its role as an intercellular communication molecule.
Competing Interests: Competing interest The authors declare that they have no competing interests.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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