In eukaryotic cells, in general, stable disulfide bonds are formed in the lumen of the RER (rough endoplasmic reticulum) and the mitochondrial intermembrane space but not in the cytosol. This is due to the more oxidizing environment of the aforementioned compartments and more reducing environment of the cytosol (see glutathione). Thus disulfide bonds are mostly found in secretory proteins, lysosomal proteins, and the exoplasmic domains of membrane proteins.
There are notable exceptions to this rule. For example, many nuclear and cytosolic proteins can become disulfide-crosslinked during necrotic cell death. Similarly, a number of cytosolic proteins which have cysteine residues in proximity to each other that function as oxidation sensors or redox catalysts; when the reductive potential of the cell fails, they oxidize and trigger cellular response mechanisms. The virus Vaccinia also produces cytosolic proteins and peptides that have many disulfide bonds; although the reason for this is unknown presumably they have protective effects against intracellular proteolysis machinery.
Disulfide bonds are also formed within and between protamines in the sperm chromatin of many mammalian species.