Disulphide maintenance systems and proteostasis

Protein disulphide formation between cysteine residues impacts protein folding and function, yet the context in which it occurs often determines whether it is beneficial or detrimental. To ensure proper disulphide status, organisms have evolved compartment-specific disulphide maintenance systems. Some of these, like the thioredoxin and glutaredoxin systems, promote disulphide reduction in oxidized substrates, whereas others, like the protein disulphide isomerase, Mia40 and Dsb systems, primarily oversee proper structural disulphide formation within client proteins. Here, I review how these disulphide maintenance systems operate and explore how they fit within the proteostasis network. Each system functions in helping proteins achieve and/or retain their functional states. Along these lines, thioredoxins can prevent aggregation of some proteins and, working with holdases, regulate recovery from protein misfolding during oxidative stress. Separately, protein disulphide isomerases work collaboratively with core molecular chaperones (e.g. Hsp70 family members) to aid in protein folding, enabling the correct formation of structural disulphides in clients. In addition, some disulphide maintenance enzymes influence protein degradation of improperly folded proteins by the proteasome. This review highlights several key ways that protein disulphide maintenance and proteostasis go hand-in-hand. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.