Endoplasmic reticulum-mitochondria junction is required for iron homeostasis

J Biol Chem. 2017 Aug 11;292(32):13197-13204. doi: 10.1074/jbc.M117.784249. Epub 2017 Jun 21.

Abstract

The endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES) is a protein complex that physically tethers the two organelles to each other and creates the physical basis for communication between them. ERMES functions in lipid exchange between the ER and mitochondria, protein import into mitochondria, and maintenance of mitochondrial morphology and genome. Here, we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell. This function is independent of known ERMES roles in calcium regulation, phospholipid biosynthesis, or effects on mitochondrial morphology. A mutation in the vacuolar protein sorting 13 (VPS13) gene that rescues the glycolytic phenotype of ERMES mutants suppresses the iron deficiency response and iron accumulation. Our findings reveal that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels.

Keywords: endoplasmic reticulum (ER); iron metabolism; mitochondria; protein import; respiration.

Publication types

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

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / metabolism*
  • Energy Metabolism
  • Gene Deletion
  • Gene Expression Regulation, Fungal
  • Homeostasis
  • Iron / analysis
  • Iron / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondria / chemistry
  • Mitochondria / metabolism*
  • Models, Biological*
  • Point Mutation
  • Protein Transport
  • RNA, Fungal / chemistry
  • RNA, Fungal / metabolism
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Analysis, RNA
  • Spectrophotometry, Atomic

Substances

  • Membrane Proteins
  • RNA, Fungal
  • RNA, Messenger
  • SAM37 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • VPS13 protein, S cerevisiae
  • Iron