Scientists have recently discovered a new strategy to repair ribosomes that get damaged due to oxidative stress. The study, published in the journal Molecular Cell, explains how oxidative stress, caused by reactive oxygen molecules, can damage ribosomes and halt the process of protein building. The discovery may affect various fields, such as cancer, growth, development, and aging.
“Literally more than half the mass of all cells are ribosomes,” says study lead author, molecular biologist Katrin Karbstein, Ph.D., a professor at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology. “If you don’t have enough ribosomes, or they are malfunctioning, proteins aren’t made correctly, and that can lead to all these diseases. We know that defects in the machinery of ribosomes are found in all cancer cells, for example.”
Though damaged items are usually cut up and recycled, completely destroying ribosomes is not feasible due to their importance in protein synthesis. The researchers found that ribosomes have an alternative way of fixing the damage with “helper molecules” that work like chaperones. These molecules escort the damaged segment away from the cell, help repair the damage, and send the ribosome back to resume work.
Wertheim UF Scripps Institute chemist Kate Carroll, Ph.D., and her lab developed special reagents and processes for monitoring oxidative damage to cystine amino acids, which made the current biochemical studies possible. The researchers have many additional questions they hope to investigate, such as discovering more chaperones and exploring how bacterial repair mechanisms help them evade antibiotics.
These results found that cysteines in Rps26 and Rpl10 are readily oxidized, rendering the proteins non-functional. Oxidized Rps26 and Rpl10 are released from ribosomes by their chaperones, Tsr2 and Sqt1, and the damaged ribosomes are subsequently repaired with newly made proteins. Ablation of this pathway impairs growth, which is exacerbated under oxidative stress.
Identification of these ribosome repair mechanisms, as well as chaperones’ ability to help them fix oxidative damage, can hopefully help scientists and researchers further understand the aging process, growth, development, and cancer.