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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.
KeywordsEndoplasmic reticulum (ER)-Mitochondria-Mitochondria-associated membrane (MAM)-Oxidative protein folding-Ero1α
Cell Stress and Chaperones 04/2012; 15(5):619-629. · 3.01 Impact Factor
