Two phases of disulfide bond formation have differing requirements for oxygen

• DOI: 10.1083/jcb.201307185
• Publication Date: 2013-11-19T04:58:24Z
• Authors: Marianne Koritzinsky; Fiana Levitin; Twan van den Beucken; Ryan A. Rumantir; Nicholas J. Harding; Kenneth C. Chu; Paul C. Boutros; Ineke Braakman; Bradly G. Wouters
• Keywords: electron; Protein Folding; glycosylation; protein synthesis; Transcription, Genetic; Messenger; 612; Endoplasmic Reticulum; Medical and Health Sciences; Models, Biological; isomerization; 03 medical and health sciences; Genetic; Isomerism; Models; protein folding; Humans; human; Disulfides; RNA, Messenger; Protein Processing; Research Articles; glycan; 0303 health sciences; hypoxia; human cell; Post-Translational; article; Biological Sciences; Biological; HCT116 Cells; Cell Hypoxia; 3. Good health; Oxygen; endoplasmic reticulum; priority journal; Hela Cells; endoplasmic reticulum stress; RNA; disulfide bond; Generic health relevance; mammal cell; Transcription; oxygen; Protein Processing, Post-Translational; Developmental Biology; HeLa Cells

Most proteins destined for the extracellular space require disulfide bonds folding and stability. Disulfide are introduced co- post-translationally in endoplasmic reticulum (ER) cargo a redox relay that requires terminal electron acceptor. Oxygen can serve as acceptor vitro, but its role vivo remains unknown. Hypoxia causes ER stress, suggesting oxygen protein folding. Here we demonstrate existence of two phases bond formation living mammalian cells, with differential requirements oxygen. rapidly during synthesis occur without oxygen, whereas those post-translational or isomerization dependent. Other maturation processes secretory pathway, including ER-localized N-linked glycosylation, glycan trimming, Golgi-localized complex transport, independently availability. These results suggest an alternative is available transiently initial phase oxygen-dependent hypoxia-induced stress.