Abstract
The way in which Drosophila melanogaster acquires iron from the diet remains poorly understood despite iron absorption being of vital significance for larval growth. To describe the process of organismal iron absorption, consideration needs to be given to cellular iron import, storage, export and how intestinal epithelial cells sense and respond to iron availability. Here we review studies on the Divalent Metal Transporter-1 homolog Malvolio (iron import), the recent discovery that Multicopper Oxidase-1 has ferroxidase activity (iron export) and the role of ferritin in the process of iron acquisition (iron storage). We also describe what is known about iron regulation in insect cells. We then draw upon knowledge from mammalian iron homeostasis to identify candidate genes in flies. Questions arise from the lack of conservation in Drosophila for key mammalian players, such as ferroportin, hepcidin and all the components of the hemochromatosis-related pathway. Drosophila and other insects also lack erythropoiesis. Thus, systemic iron regulation is likely to be conveyed by different signaling pathways and tissue requirements. The significance of regulating intestinal iron uptake is inferred from reports linking Drosophila developmental, immune, heat-shock and behavioral responses to iron sequestration.
Highlights
This review focuses on studies that involved Drosophila melanogaster, it is important to highlight at the outset a number of excellent review articles that describe relevant studies in other insects [51,52,53], including recent publications focusing on insect iron-storage ferritin complexes [54]
Our own investigations on whether heme biosynthetic genes were required in ―circadian‖ neurons were inconclusive; instead we discovered that iron-sulfur cluster biosynthesis genes were implicated in the maintenance of circadian rhythms [94]
Drosophila shares with mammals the following proteins that function in iron absorption: Mvl (DMT1 homolog; iron import), ferritin, Iron Regulatory Proteins (IRPs)-1A, MCO1/MCO3, Tsf1 and Tsf2
Summary
Iron is an indispensible micronutrient for the development of Drosophila melanogaster [1,2]. Heme or iron-sulfur clusters carry out numerous physiological functions, including respiration [3] and the synthesis of DNA [4,5], ecdysone [6,7], dopamine [8] and lipids [9]. Despite the elucidation of key biochemical requirements for iron, our knowledge of how iron is acquired from the diet of Drosophila larvae or adults and distributed to its various target tissues and proteins in a regulated manner remains at a rudimentary level [15]. We identify key genes that are conserved between Drosophila and mammals and are predicted to function in iron absorption. Some of the players with known roles in mammals are not conserved in Drosophila. The immune response, the maintenance of circadian rhythms and a number of developmental and aging-related processes are known to depend on iron, meaning that further research into iron homeostasis in the Drosophila model is required
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