Proteostasis

Definition

Proteostasis, short for protein homeostasis, is the set of cellular processes that maintain the quality, quantity, folding, trafficking, and degradation of proteins. It depends on systems such as molecular chaperones, the ubiquitin-proteasome system, autophagy, and stress-response pathways that help cells prevent, repair, or remove damaged and misfolded proteins. [1] [2] [3]

Why It Matters in Ageing Research

Proteostasis matters because proteins must remain correctly folded and functional for cells and tissues to work properly. With ageing, protein quality-control systems can become less effective, allowing damaged, misfolded, or aggregated proteins to accumulate. Loss of proteostasis is considered one of the hallmarks of ageing and is especially relevant to age-related diseases in which protein aggregation or impaired protein clearance plays a role. [2] [4] [5]

Common Confusion

• Proteostasis is not one pathway; it is a network of protein quality-control systems.
• Loss of proteostasis does not mean all proteins are damaged, but that maintenance systems are less effective.
• Protein aggregation is one sign of proteostasis failure, but proteostasis also includes folding, repair, transport, and degradation.

Related Reading

• Autophagy

References

1. Balch, W. E., et al. (2008). Adapting proteostasis for disease intervention. https://pubmed.ncbi.nlm.nih.gov/18413248/
2. Powers, E. T., et al. (2009). Biological and chemical approaches to diseases of proteostasis deficiency. https://pubmed.ncbi.nlm.nih.gov/19625408/
3. Labbadia, J., & Morimoto, R. I. (2015). The biology of proteostasis in aging and disease. https://pubmed.ncbi.nlm.nih.gov/25710535/
4. López-Otín, C., et al. (2013). The hallmarks of aging. https://pubmed.ncbi.nlm.nih.gov/23746838/
5. Hipp, M. S., et al. (2019). Proteostasis impairment in protein-misfolding and aggregation diseases. https://pubmed.ncbi.nlm.nih.gov/31388181/