About Proteostasis

What is proteostasis?

Maintaining protein homeostasis or proteostasis is important in the normal ‘housekeeping’ of the body.

The control of protein homeostasis heavily relies on molecular chaperones and protein degradation. However, in reality, there are many processes in place to ensure that proteostasis is maintained. In order to produce a properly functioning protein, the processes of transcription, RNA processing and transport, translation, protein folding, protein transport and ultimately protein degradation must be tightly regulated.

Proteostasis as a closed system

Proteostasis can be thought of as a closed system with a finite ‘capacity’, although the capacity or volume of the system can be changed and altered by increasing or decreasing the concentration of its components (such as molecular chaperones).

Overloading the system

Under normal conditions the capacity of the system is enough to maintain proteostasis. However, there are a number of ways to overload this. Genetic mutations that increase the propensity of a peptide or protein to aggregate would increase the workload of a number of components of the system, and may exceed its capacity. However, it appears that an additional co-incident strain on any other protein homeostasis mechanism can add to the cumulative workload and result in the capacity of the system as a whole being exceeded.

Overload and disease

This may explain the age-related appearance of insoluble protein deposits associated with a range of diseases (including amyloidosis and motor neurone disease), even though the involved proteins are initially effectively maintained in a soluble and fully functional state. Given the intimate link between dysfunctions of proteostasis and many serious diseases it is imperative that research in this area is continued and expanded.