What is proteostasis?
Proteostasis is the name we give to the processes that cells do in order to have all their proteins functioning properly, which in turn makes cells work properly. Since cells are the building blocks of an organism – such as ourselves – when all the cells of our body work properly, we are healthy. When proteostasis is not maintained, cells malfunction and may die, with the final outcome for the organism being cancer, neurodegeneration, inflammation, aging, developmental defects, etc.
Structure versus function?
Cells spend an enormous amount of energy to maintain the information and the structure of their molecules. Nucleic acids hold the basic information and mediate storage, retrieval, and transmission to daughter cells. In contrast, proteins are the main interpretors and executors of this information. Therefore, ensuring that proteins are doing their job properly, in the right place at the right time, is crucial for the cell and, thus, for the organism.
What does proteostasis entail?
Proteostasis relies on a tightly controlled regulation of protein fate. Proteins exert functions, but to do so they must be properly folded to interact with the right partners. Old, mutant or misfolded proteins must be recognized and degraded, and there is a continuous cellular protein turnover. But then, how are proteins recognized? Cells use a kind of post-it tag to mark proteins. There is a diversity of tags (post-translational modifications, such as ubiquitination, SUMOylation, NEDDylation, etc.) that control the final protein fate, activity and “social” life. These post-it tags are dynamic and reversible: you can attach and detach the tag. Imagine your home: you need to sort out things that you wish to throw out from those that you wish to keep. Even more, you sort them by type, as paper, plastic or glass for recycling. Any alteration in this process would eventually clutter your home with useless material. Likewise, cells also tag proteins for degradation to the proteasome. When proteins aggregate, they cannot be degraded and accumulate inside the cell, clogging it, hampering its function and eventually triggering its death by apoptosis. This is one of the common causes of neurodegeneration. On the other hand, when the sorting process is not functioning properly, cells can throw out what is still in use or be fooled into using incorrect proteins or altered pathways, thus causing cancer.
In other cases, post-it tags are attached to sort proteins into different subcellular compartments. These tags are similar to those attached to your suitcases at the airport. Workers in the baggage hall recognize each specific tag and routes each suitcase to the correct baggage carrousel. Lots of inconveniences occur when the suitcases are not sent to the right place. Similarly, cells also tag proteins so that they are properly targeted to the location where they exert their functions. Protein mislocalization leads to cellular malfunction and thus, disease.
This is just a small “taste” of why cells use a panoply of attaching (conjugating) and detaching (deconjugating) enzymes with a highly tuned specificity to respond to cellular requirements. And this is also why proteostasis is so relevant, from basic biomedical research to focused biotechnological and clinical applications. Proteostasis is at the core of many diseases that can affect us all. Only by understanding proteostasis, we can learn how to intervene and, hopefully, treat or cure these diseases.