Oxidative folding in the endoplasmic reticulum: Towards a multiple oxidant hypothesis?

Oxidative protein folding in the luminal compartment of the endoplasmic reticulum is thought to be mediated by a proteinaceous electron relay system composed by PDI and ER oxidoreductin 1 (Ero1), transferring electrons from the cysteinyl residues of substrate proteins to oxygen. However, recent observations revealed that Ero1 isoforms are dispensable. Endoplasmic reticulum is known as a generator and accumulator of low molecular weight oxidants; some of them have already been shown to promote oxidative folding. On the basis of these observations a new theory of oxidative folding is proposed where the oxidative power is provided by the stochastic contribution of prooxidants.