Ferritin is the key to dietary iron absorption and tissue iron detoxification inDrosophila melanogaster

Abstract

Mammalian ferritin is predominantly in the cytosol, with a minor portion found in plasma. In most insects, including Drosophila melanogaster, ferritin belongs to the secretory type. The functional role of secretory ferritin in iron homeostasis remains poorly understood in insects as well as in mammalians. Here we used Drosophila to dissect the involvement of ferritin in insect iron metabolism. Midgut-specific knockdown of ferritin resulted in iron accumulation in the gut but systemic iron deficiency (37% control), accompanied by retarded development and reduced survival (3% survival), and was rescued by dietary iron supplementation (50% survival) or exacerbated by iron depletion (0% survival). These results suggest an essential role of ferritin in removing iron from enterocytes across the basolateral membrane. Expression of wild-type ferritin in the midgut, especially in the iron cell region, could significantly rescue ferritin-null mutants (first-instar larvae rescued up to early adults), indicating iron deficiency as the major cause of early death for ferritin flies. In many nonintestinal tissues, tissue-specific ferritin knockdown also caused local iron accumulation (100% increase) and resulted in severe tissue damage, as evidenced by cell loss. Overall, our study demonstrated Drosophila ferritin is essential to two key aspects of iron homeostasis: dietary iron absorption and tissue iron detoxification.

Serum IL8 and mRNA level of CD11b in circulating neutrophils are increased in clinically amyopathic dermatomyositis with active interstitial lung disease

“…Evidences suggested that the origin of serum ferritin must indeed largely, if not entirely, be seen as cellular damage, that is to say it is mainly a leakage product from damaged cells. Ferritin is genuinely secreted, as it is for instance in insects [41][42][43], and mammalian does not have suitable leader (secretion signal) sequences for ferritin secretion. There is no any actual evidence for regulated or active secretion of ferritin in humans in vivo.…”

The Digestive Tract of Drosophila melanogaster

“…Iron uptake is, in part, mediated by the divalent transporter ion transporter 1 (DMT1) homolog Malvolio (11). In addition to their role in iron storage, ferritins also mediate iron export from the midgut to the hemolymph (107,181). Finally, zinc absorption is mediated by ZIP transporters, whereas zinc efflux from the cytoplasm to the hemolymph is mediated by ZnT transporters.…”

Mitoferrin modulates iron toxicity in a Drosophila model of Friedreich׳s ataxia

“…Fer1HCH and Fer2LCH coassemble to holoferritin to store iron [26]. However, in contrast to mammals, fly ferritin localizes to the endoplasmic reticulum and the Golgi complex and it is secreted to the hemolymph for iron sequestration/transport [26,27]. Fer3HCH is the ortholog to mammalian mitochondrial ferritin [28].…”