Ferritin Assembly in Enterocytes of Drosophila melanogaster

Abstract

Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH) and Ferritin 2 Light Chain Homolog (Fer2LCH) are further stabilized by disulfide-bridge in the 24-subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH-Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated.

miR-425-5p Inhibits Differentiation and Proliferation in Porcine Intramuscular Preadipocytes

“…Krüppel-like factors (KLFs) are important regulators of cell differentiation, proliferation, and a number of other cellular processes [ 32 ]. In recent years, a total of 10 KLF proteins (KLF2-9, KLF13, and KLF15) have been proved to either promote or inhibit adipocyte differentiation [ 22 , 31 ]. Specifically, KLF13 has been proved to be a key pro-adipogenic factor through regulating PPARγ transactivation at the early stage of porcine adipocyte differentiation [ 31 ].…”

“…Recently, many studies have indicated that miRNAs play key roles in regulating adipogenesis [ 11 ]. In porcine adipogenesis, miR-103, miR-181a, miR-15a/b, miR-196a, miR-17, miR-21, miR-143, and miR-146a-5p promoted porcine preadipocyte differentiation [ 12 , 13 , 14 , 15 , 16 , 17 ], while miR-125a, miR-145, miR-191, miR-199a-5p, miR-375, and miR-429 impaired porcine preadipocyte differentiation [ 18 , 19 , 20 , 21 , 22 , 23 ].…”

Biogenesis of zinc storage granules inDrosophila melanogaster

“…In Drosophila, iron availability is linked to key developmental signals, such as ecdysone synthesis (Llorens et al, 2015;Palandri et al, 2015), and to processes such as the formation of epithelial septate junctions (Tiklová et al, 2010), the functionality of the circadian clock (Mandilaras and Missirlis, 2012), and the induction of mitotic events (Li, 2010). So far, a single iron transporter moving iron into the cytosol has been identified in flies (Orgad et al, 1998;Bettedi et al, 2011) and a single iron exporter has been suggested to traffic iron from the cytosol into the endoplasmic reticulum and Golgi apparatus (Xiao et al, 2014), where insect ferritin resides (Missirlis et al, 2007;Rosas-Arellano et al, 2016).…”

Loss of ferritin in developing wing cells: Apoptosis and ferroptosis coincide

“…Why is it then that interference with ferritin H function in some cells produces stronger phenotypes [1,22,29], while the converse is also true (i.e., ferritin L specific phenotypes [30] also exist)? We hypothesize that the reason relates to ferritin assembly regulation [31] as opposed to moonlighting functions for the individual subunits. For example, surrounding cells could provide ferritin L subunits to their neighbors but not vice versa.…”