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Oxidative folding in the endoplasmic reticulum: towards a multiple oxidant hypothesis?
Eva Margittai1, Gábor Bánhegyi
1Università Vita-Salute, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
Oxidative protein folding in the endoplasmic reticulum may not require Ero1, suggesting a new theory where prooxidants provide the necessary oxidative power for this crucial cellular process.
Area of Science:
- Cellular Biology
- Biochemistry
- Protein Folding
Background:
- Oxidative protein folding occurs in the endoplasmic reticulum.
- It is traditionally thought to involve protein disulfide isomerase (PDI) and ER oxidoreductin 1 (Ero1).
- Ero1 isoforms have recently been found to be dispensable for this process.
Purpose of the Study:
- To propose a new theory for oxidative protein folding.
- To investigate the role of low molecular weight oxidants in oxidative folding.
Main Methods:
- Review of recent observations on Ero1 dispensability.
- Analysis of the endoplasmic reticulum's known oxidant-generating capacity.
Main Results:
- Ero1 isoforms are not essential for oxidative protein folding.
- The endoplasmic reticulum generates and accumulates low molecular weight oxidants.
- These oxidants can promote oxidative folding.
Conclusions:
- A new theory of oxidative folding is proposed.
- Oxidative power may be provided by the stochastic action of prooxidants, rather than solely by the PDI-Ero1 system.
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