Cell Stress and Chaperones

, Volume 15, Issue 5, pp 619–629 | Cite as

Ero1α requires oxidizing and normoxic conditions to localize to the mitochondria-associated membrane (MAM)

  • Susanna Y. Gilady
  • Michael Bui
  • Emily M. Lynes
  • Matthew D. Benson
  • Russell Watts
  • Jean E. Vance
  • Thomas Simmen
Original Paper

Abstract

Protein secretion from the endoplasmic reticulum (ER) requires the enzymatic activity of chaperones and oxidoreductases that fold polypeptides and form disulfide bonds within newly synthesized proteins. The best-characterized ER redox relay depends on the transfer of oxidizing equivalents from molecular oxygen through ER oxidoreductin 1 (Ero1) and protein disulfide isomerase to nascent polypeptides. The formation of disulfide bonds is, however, not the sole function of ER oxidoreductases, which are also important regulators of ER calcium homeostasis. Given the role of human Ero1α in the regulation of the calcium release by inositol 1,4,5-trisphosphate receptors during the onset of apoptosis, we hypothesized that Ero1α may have a redox-sensitive localization to specific domains of the ER. Our results show that within the ER, Ero1α is almost exclusively found on the mitochondria-associated membrane (MAM). The localization of Ero1α on the MAM is dependent on oxidizing conditions within the ER. Chemical reduction of the ER environment, but not ER stress in general leads to release of Ero1α from the MAM. In addition, the correct localization of Ero1α to the MAM also requires normoxic conditions, but not ongoing oxidative phosphorylation.

Keywords

Endoplasmic reticulum (ER) Mitochondria Mitochondria-associated membrane (MAM) Oxidative protein folding Ero1α 

Abbreviations

2ME

2-mercaptoethanol

BiP/GRP78

Immunoglobulin binding protein/glucose-regulated protein of 78 kDa

Ero1α

ER oxidoreductin 1

HEK

Human embryonic kidney

MAM

Mitochondria-associated membrane

PACS-2

Phospho-furin acidic cluster sorting protein 2

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Copyright information

© Cell Stress Society International 2010

Authors and Affiliations

  • Susanna Y. Gilady
    • 1
  • Michael Bui
    • 1
  • Emily M. Lynes
    • 1
  • Matthew D. Benson
    • 1
  • Russell Watts
    • 2
  • Jean E. Vance
    • 2
  • Thomas Simmen
    • 1
  1. 1.Department of Cell BiologyUniversity of AlbertaEdmontonCanada
  2. 2.Group on the Molecular and Cell Biology of Lipids, Department of MedicineUniversity of AlbertaEdmontonCanada

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