Oxidation and reduction of cysteines in the intermembrane space of mitochondria: multiple facets of redox control.

Eukaryotic cells employ a large variety of protein modifications to integrate individual protein activities into regulatory or signaling networks. Thereby, different compartments prefer specific types of protein modifications. For example, protein phosphorylation is a highly frequent modification in the cytosol and the nucleus, whereas in the lumen of the endoplasmic reticulum, protein functions may be predominantly regulated by protein oxidation or glycosylation. On the hundreds of mitochondrial proteins, only very few modifications were reported until very recently. This is particularly true for proteins of the intermembrane space, the compartment between the outer and inner membrane. However, studies over the last 5 years suggest that the introduction of disulfide bonds might regulate a variety of processes in this compartment. The different processes for which such redox regulations were shown or proposed include the import and folding of proteins and the assembly of cofactors of respiratory chain complexes. Although the understanding of the molecular functions underlying these processes is rapidly increasing, we still do hardly understand how these redox activities are used to coordinate mitochondrial activities with cellular functions such as apoptosis, reactive oxygen species homeostasis, or aging.