Specific iron chelators determine the route of ferritin degradation.

Abstract:

:Deferoxamine (DFO) is a high-affinity Fe (III) chelator produced by Streptomyces pilosus. DFO is used clinically to remove iron from patients with iron overload disorders. Orally administered DFO cannot be absorbed, and therefore it must be injected. Here we show that DFO induces ferritin degradation in lysosomes through induction of autophagy. DFO-treated cells show cytosolic accumulation of LC3B, a critical protein involved in autophagosomal-lysosomal degradation. Treatment of cells with the oral iron chelators deferriprone and desferasirox did not show accumulation of LC3B, and degradation of ferritin occurred through the proteasome. Incubation of DFO-treated cells with 3-methyladenine, an autophagy inhibitor, resulted in degradation of ferritin by the proteasome. These results indicate that ferritin degradation occurs by 2 routes: a DFO-induced entry of ferritin into lysosomes and a cytosolic route in which iron is extracted from ferritin before degradation by the proteasome.

journal_name

Blood

journal_title

Blood

authors

De Domenico I,Ward DM,Kaplan J

doi

10.1182/blood-2009-05-224188

subject

Has Abstract

pub_date

2009-11-12 00:00:00

pages

4546-51

issue

20

eissn

0006-4971

issn

1528-0020

pii

blood-2009-05-224188

journal_volume

114

pub_type

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