Biogenesis and functions of mammalian iron-sulfur proteins in the regulation of iron homeostasis and pivotal metabolic pathways

J Biol Chem. 2017 Aug 4;292(31):12744-12753. doi: 10.1074/jbc.R117.789537. Epub 2017 Jun 14.

Abstract

Fe-S cofactors are composed of iron and inorganic sulfur in various stoichiometries. A complex assembly pathway conducts their initial synthesis and subsequent binding to recipient proteins. In this minireview, we discuss how discovery of the role of the mammalian cytosolic aconitase, known as iron regulatory protein 1 (IRP1), led to the characterization of the function of its Fe-S cluster in sensing and regulating cellular iron homeostasis. Moreover, we present an overview of recent studies that have provided insights into the mechanism of Fe-S cluster transfer to recipient Fe-S proteins.

Keywords: HSC20; HSPA9; ISCU; energy metabolism; iron-response element (IRE); iron-sulfur cluster biogenesis; iron-sulfur protein; metalloenzyme; mitochondrial respiratory chain complex.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoenzymes / chemistry
  • Apoenzymes / metabolism
  • Carbon-Sulfur Lyases / biosynthesis
  • Carbon-Sulfur Lyases / chemistry
  • Carbon-Sulfur Lyases / physiology
  • Electron Transport
  • Frataxin
  • Gene Expression Regulation, Enzymologic
  • HSP70 Heat-Shock Proteins / biosynthesis
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / physiology
  • Homeostasis*
  • Humans
  • Iron / physiology*
  • Iron Regulatory Protein 1 / biosynthesis
  • Iron Regulatory Protein 1 / chemistry
  • Iron Regulatory Protein 1 / physiology*
  • Iron-Binding Proteins / biosynthesis
  • Iron-Binding Proteins / chemistry
  • Iron-Binding Proteins / physiology
  • Iron-Regulatory Proteins / biosynthesis
  • Iron-Regulatory Proteins / chemistry
  • Iron-Regulatory Proteins / physiology
  • Iron-Sulfur Proteins / biosynthesis
  • Iron-Sulfur Proteins / chemistry
  • Iron-Sulfur Proteins / physiology
  • Mitochondrial Proteins / biosynthesis
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / physiology
  • Models, Molecular*
  • Molecular Chaperones / biosynthesis
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / physiology
  • Protein Folding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Response Elements
  • Succinate Dehydrogenase / biosynthesis
  • Succinate Dehydrogenase / chemistry
  • Succinate Dehydrogenase / physiology

Substances

  • Apoenzymes
  • HSCB protein, human
  • HSP70 Heat-Shock Proteins
  • HSPA9 protein, human
  • ISCU protein, human
  • Iron-Binding Proteins
  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins
  • LYRM4 protein, human
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Iron
  • SDHB protein, human
  • Succinate Dehydrogenase
  • ACO1 protein, human
  • Iron Regulatory Protein 1
  • Carbon-Sulfur Lyases
  • NFS1 protein, human

Associated data

  • PDB/3SFD