Insect ferritins: Typical or atypical?

Abstract

Insects transmit millions of cases of disease each year, and cost millions of dollars in agricultural losses. The control of insect-borne diseases is vital for numerous developing countries, and the management of agricultural insect pests is a very serious business for developed countries. Control methods should target insect-specific traits in order to avoid non-target effects, especially in mammals. Since insect cells have had a billion years of evolutionary divergence from those of vertebrates, they differ in many ways that might be promising for the insect control field—especially, in iron metabolism because current studies have indicated that significant differences exist between insect and mammalian systems. Insect iron metabolism differs from that of vertebrates in the following respects. Insect ferritins have a heavier mass than mammalian ferritins. Unlike their mammalian counterparts, the insect ferritin subunits are often glycosylated and are synthesized with a signal peptide. The crystal structure of insect ferritin also shows a tetrahedral symmetry consisting of 12 heavy chain and 12 light chain subunits in contrast to that of mammalian ferritin that exhibits an octahedral symmetry made of 24 heavy chain and 24 light chain subunits. Insect ferritins associate primarily with the vacuolar system and serve as iron transporters—quite the opposite of the mammalian ferritins, which are mainly cytoplasmic and serve as iron storage proteins. This review will discuss these differences.

Iron depletion in the intestines ofMalvoliomutant flies does not occur in the absence of a multicopper oxidase

“…Additionally, we found that administration of 1mmoll -1 CuSO 4 not only led to a dramatic tenfold accumulation of copper ( Fig.1B) but also decreased iron accumulation in w control flies (Fig.1A) decrease in total body iron was also seen in Mvl 97f mutant flies, but they accumulated iron to similar levels as the controls when the diet was supplemented with 1mmoll -1 FAC (Fig.1A). As an independent readout of iron uptake we analyzed the incorporation of iron into ferritin, the major iron storage protein in Drosophila (Pham and Winzerling, 2010). We have previously demonstrated that iron-loaded ferritin remains stable under nonreducing conditions, in the presence of SDS Missirlis et al, 2007).…”

“…As a consequence, some aspects of systemic iron homeostasis, defined as all movement of iron in the organism, and regulatory mechanisms that control this movement maintaining an overall stable condition (Hentze et al, 2004;Nichol et al, 2002), may differ between invertebrates and vertebrates. Nevertheless, key proteins involved in iron regulation have conserved functions as exemplified by the ferritins Missirlis et al, 2007;Pham and Winzerling, 2010), the iron regulatory proteins (Lind et al, 2006) and the transferrins Tiklová et al, 2010). We became interested in the DMT1 homologue in Drosophila melanogaster, encoded by the Mvl gene, originally identified in a mutagenesis screen designed to identify genes affecting taste behaviour in flies (Rodrigues et al, 1995).…”

Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster

“…Given that ferroxidases are necessary for iron metabolism in a diverse set of organisms (2,3,6,7,13,14), it seemed likely that they would exist in insects. On the contrary, the multicopper ferroxidases with known physiological functions work in conjunction with an iron permease (2-5), whereas we and others have been unable to identify an iron permease gene in any insect genome (9).…”

“…Divalent metal transporter 1 (DMT1) transports iron from the diet into midgut epithelial cells (8). Ferritin has two functions in insects: iron storage (comparable to the function of mammalian ferritin) and iron transport (9). Insect ferritin is present in the endoplasmic reticulum and Golgi complex of a variety of cell types, including midgut cells, and iron-loaded ferritin is secreted into the hemolymph and is thought to transport iron to other parts of the body (9).…”

“…Ferritin has two functions in insects: iron storage (comparable to the function of mammalian ferritin) and iron transport (9). Insect ferritin is present in the endoplasmic reticulum and Golgi complex of a variety of cell types, including midgut cells, and iron-loaded ferritin is secreted into the hemolymph and is thought to transport iron to other parts of the body (9). Insect transferrin is present in the hemolymph, and, like mammalian transferrin, it may function as an iron transport protein (10,11), although the mechanism of ferrictransferrin uptake is unknown (12).…”