caa a22 4500 605507554 CHVBK 20210128100632.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00775-015-1302-2 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1302-2 Mitochondrial iron supply is required for the developmental pulse of ecdysone biosynthesis that initiates metamorphosis in Drosophila melanogaster [Elektronische Daten] [Jose Llorens, Christoph Metzendorf, Fanis Missirlis, Maria Lind] Synthesis of ecdysone, the key hormone that signals the termination of larval growth and the initiation of metamorphosis in insects, is carried out in the prothoracic gland by an array of iron-containing cytochrome P450s, encoded by the halloween genes. Interference, either with iron-sulfur cluster biogenesis in the prothoracic gland or with the ferredoxins that supply electrons for steroidogenesis, causes a block in ecdysone synthesis and developmental arrest in the third instar larval stage. Here we show that mutants in Drosophila mitoferrin (dmfrn), the gene encoding a mitochondrial carrier protein implicated in mitochondrial iron import, fail to grow and initiate metamorphosis under dietary iron depletion or when ferritin function is partially compromised. In mutant dmfrn larvae reared under iron replete conditions, the expression of halloween genes is increased and 20-hydroxyecdysone (20E), the active form of ecdysone, is synthesized. In contrast, addition of an iron chelator to the diet of mutant dmfrn larvae disrupts 20E synthesis. Dietary addition of 20E has little effect on the growth defects, but enables approximately one-third of the iron-deprived dmfrn larvae to successfully turn into pupae and, in a smaller percentage, into adults. This partial rescue is not observed with dietary supply of ecdysone's precursor 7-dehydrocholesterol, a precursor in the ecdysone biosynthetic pathway. The findings reported here support the notion that a physiological supply of mitochondrial iron for the synthesis of iron-sulfur clusters and heme is required in the prothoracic glands of insect larvae for steroidogenesis. Furthermore, mitochondrial iron is also essential for normal larval growth. SBIC, 2015 Development nationallicence Insect nationallicence Mitochondria nationallicence Mitoferrin nationallicence Cholesterol nationallicence 7DHC : 7-dehydrocholesterol nationallicence 20E : 20-hydroxyecdysone nationallicence BPS : Bathophenanthroline disulfonate nationallicence dfh : Drosophila frataxin nationallicence dib : disembodied nationallicence dmfrn : Drosophila mitoferrin nationallicence E74A : Ecdysone-induced protein 74EF nationallicence FAC : Ferric ammonium citrate nationallicence Fer1HCH : Ferritin 1 heavy chain homolog nationallicence GFP : Green fluorescent protein nationallicence Gp93 : Glycoprotein 93 nationallicence Hsc20 : Heat shock protein cognate 2 nationallicence MRS3/4 : Yeast mitoferrins nationallicence RNAi : RNA interference nationallicence Rp49 : Ribosomal protein L32 nationallicence sad : shadow nationallicence Tb : Tubby nationallicence Llorens Jose Department of Comparative Physiology, Uppsala University, Norbyvägen 18A, Uppsala, Sweden aut Metzendorf Christoph Heidelberg University Biochemistry Center (BZH), University of Heidelberg, Im Neuenheimer Feld 328, Heidelberg, Germany aut Missirlis Fanis Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. IPN 2508, Mexico City, Mexico aut Lind Maria Department of Comparative Physiology, Uppsala University, Norbyvägen 18A, Uppsala, Sweden aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/8(2015-12-01), 1229-1238 0949-8257 20:8<1229 2015 20 775 https://doi.org/10.1007/s00775-015-1302-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1302-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Llorens Jose Department of Comparative Physiology, Uppsala University, Norbyvägen 18A, Uppsala, Sweden aut NATIONALLICENCE 700 1- Metzendorf Christoph Heidelberg University Biochemistry Center (BZH), University of Heidelberg, Im Neuenheimer Feld 328, Heidelberg, Germany aut NATIONALLICENCE 700 1- Missirlis Fanis Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. IPN 2508, Mexico City, Mexico aut NATIONALLICENCE 700 1- Lind Maria Department of Comparative Physiology, Uppsala University, Norbyvägen 18A, Uppsala, Sweden aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/8(2015-12-01), 1229-1238 0949-8257 20:8<1229 2015 20 775