Caenorhabditis elegans ATAD-3 modulates mitochondrial iron and heme homeostasis

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

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.

Keywords: Heme; Iron; Metabolism; Mitochondria; Oxidative phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Ferric Compounds / pharmacology
  • Gene Expression Regulation
  • Heme / metabolism*
  • Hemeproteins / genetics
  • Hemeproteins / metabolism
  • Hemin / metabolism
  • Homeostasis
  • Iron / metabolism*
  • Mitochondria / drug effects
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondrial Proteins / antagonists & inhibitors
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Oxidative Phosphorylation / drug effects
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Quaternary Ammonium Compounds / pharmacology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction

Substances

  • Caenorhabditis elegans Proteins
  • Ferric Compounds
  • Hemeproteins
  • Mitochondrial Proteins
  • Protein Isoforms
  • Quaternary Ammonium Compounds
  • RNA, Small Interfering
  • atad-3 protein, C elegans
  • hrg-2 protein, C elegans
  • Heme
  • Hemin
  • Iron
  • ferric ammonium citrate