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Redox diversity in ERAD-mediated protein retrotranslocation from the endoplasmic reticulum: a complex puzzle

  • Yutaka Suzuki und Manfred J. Schmitt EMAIL logo
Veröffentlicht/Copyright: 28. Februar 2015

Abstract

Misfolded and incorrectly assembled proteins in the secretory pathway are eliminated by ubiquitylation and proteasomal degradation in a process known as ER-associated degradation (ERAD). Retrotranslocation of diverse substrates including misfolded proteins and viruses occurs through channels in the ER membrane, which are also utilized for host cell penetration by A/B class protein toxins such as cholera toxin, ricin or K28. According to the current view, disulfide-bonded proteins must either be reduced or rearranged to ensure translocation competence and entry into the cytosol from the ER. As the underlying mechanisms are still largely mysterious, we here focus on the redox status and disulfide isomerization of ERAD substrates and the role of oxidoreductases in the essential process of ER-to-cytosol retrotranslocation.


Corresponding author: Manfred J. Schmitt, Molecular and Cell Biology, Department of Biosciences and Center of Human and Molecular Biology (ZHMB), Saarland University, Campus Building A 1.5, D-66123 Saarbrücken, Germany, e-mail:

Acknowledgments

M.J.S. kindly acknowledges support by the Deutsche Forschungsgemeinschaft within priority program SPP 1710.

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Received: 2014-12-8
Accepted: 2015-2-23
Published Online: 2015-2-28
Published in Print: 2015-5-1

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