title: Caenorhabditis elegans ATAD-3 modulates mitochondrial iron and heme homeostasis.
abstract: ATAD3 (ATPase family AAA domain-containing protein 3) is a mitochondrial protein, which is essential for cell viability and organismal development. ATAD3 has been implicated in several important cellular processes such as apoptosis regulation, respiratory chain function and steroid hormone biosynthesis. Moreover, altered expression of ATAD3 has been associated with several types of cancer. However, the exact mechanisms underlying ATAD3 effects on cellular metabolism remain largely unclear. Here, we demonstrate that Caenorhabditis elegans ATAD-3 is involved in mitochondrial iron and heme homeostasis. Knockdown of atad-3 caused mitochondrial iron- and heme accumulation. This was paralleled by changes in the expression levels of several iron- and heme-regulatory genes as well as an increased heme uptake. In conclusion, our data indicate a regulatory role of C. elegans ATAD-3 in mitochondrial iron and heme metabolism.
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: van den Ecker
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Müting
authors.affiliation: Institute of Clinical Chemistry and Laboratory Diagnostic, Medical Faculty, Heinrich-Heine-University and the IUF- Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maglioni
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
authors.forename: Diran
authors.initials: D
authors.lastname: Herebian
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
authors.forename: Ertan
authors.initials: E
authors.lastname: Mayatepek
authors.affiliation: Institute of Clinical Chemistry and Laboratory Diagnostic, Medical Faculty, Heinrich-Heine-University and the IUF- Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Natascia
authors.initials: N
authors.lastname: Ventura
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address: felix.distelmaier@med.uni-duesseldorf.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Distelmaier
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology; D005786:Gene Expression Regulation; D006418:Heme / Q000378:metabolism*; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism; D006427:Hemin / Q000378:metabolism; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D005290:Ferric Compounds; D006420:Hemeproteins; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; C546126:atad-3 protein, C elegans; C572636:hrg-2 protein, C elegans; D006418:Heme; D006427:Hemin; D007501:Iron; C013531:ferric ammonium citrate
keywords: Heme; Iron; Metabolism; Mitochondria; Oxidative phosphorylation