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New iron export pathways acting via holo-ferritin secretion
Izumi Yanatori1, Fumio Kishi2, Shinya Toyokuni3
1Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
Archives of Biochemistry and Biophysics
|September 8, 2023
Summary
Cells secrete iron-storage ferritin via extracellular vesicles (EVs), acting as an intercellular iron transporter. This process, regulated by CD63 and NCOA4, impacts cellular iron levels and can cause oxidative stress in recipient cells.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Ferritin, an iron-storage protein, is crucial for preventing intracellular iron toxicity.
- Serum ferritin levels indicate total body iron stores, but cellular release mechanisms remain unclear.
- Ferritin secretion occurs via extracellular vesicles (EVs) or secretory autophagy, bypassing the ER-Golgi pathway.
Approach:
- Investigated ferritin incorporation into CD63-positive EVs mediated by NCOA4.
- Examined alternative ferritin secretion pathways in detached cells involving prominin 2-positive EVs.
- Reviewed the machinery of ferritin incorporation into EVs and its extracellular functions.
Key Points:
- Intracellular iron levels post-transcriptionally regulate CD63, a common EV marker.
- Iron loading induces both CD63 and ferritin expression.
- Ferritin secretion via EVs can be NCOA4-dependent or independent, depending on cell type and conditions.
Conclusions:
- Ferritin functions as an extracellular iron carrier within EVs.
- Secretion of holo-ferritin reduces intracellular iron but can induce oxidative stress (ROS) in recipient cells.
- Ferritin acts as an intercellular communication molecule, modulating iron availability and cellular responses.
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