秀丽隐杆线虫ATAD-3调节线粒体铁和血红素稳态。

Caenorhabditis elegans ATAD-3 modulates mitochondrial iron and heme homeostasis.

作者信息

van den Ecker Daniela, Hoffmann Michael, Müting Gesine, Maglioni Silvia, Herebian Diran, Mayatepek Ertan, Ventura Natascia, Distelmaier Felix

机构信息

Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.

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.

出版信息

Biochem Biophys Res Commun. 2015 Nov 13;467(2):389-94. doi: 10.1016/j.bbrc.2015.09.143. Epub 2015 Sep 30.

DOI:10.1016/j.bbrc.2015.09.143

PMID:26427876

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.

摘要

ATAD3（含ATP酶家族AAA结构域蛋白3）是一种线粒体蛋白，对细胞活力和机体发育至关重要。ATAD3参与了多种重要的细胞过程，如细胞凋亡调控、呼吸链功能和类固醇激素生物合成。此外，ATAD3表达改变与多种癌症相关。然而，ATAD3影响细胞代谢的确切机制仍 largely不清楚。在此，我们证明秀丽隐杆线虫的ATAD-3参与线粒体铁和血红素稳态。敲低atad-3导致线粒体铁和血红素积累。这与几种铁和血红素调节基因表达水平的变化以及血红素摄取增加同时发生。总之，我们的数据表明秀丽隐杆线虫的ATAD-3在线粒体铁和血红素代谢中起调节作用。