Proteins are the fundamental components of virtually everything occurring within our bodies – but what happens when the machines that make proteins become defective? 

These protein-making machines are called ribosomes and mutations in ribosomes are connected to a group of human disorders called ribosomopathies. However, it remains unclear, at a cellular level, why defects in ribosomes cause problems in our bodies. This is where the use of model organisms such as fruit flies for research purposes is particularly valuable.

In a recent study, scientists used the fruit fly as a model to study the cellular basis of ribosomapathy. The scientists introduced a mutation previously reported from a human patient into the fruit fly ribosome. The resulting flies were developmentally delayed, and had much shorter hairs than normal.

In looking at the fruit fly cells, the researchers found that proteins that were not produced properly built up and formed aggregates. Proteins have to be folded into the correct 3D structure to perform their functions; and cells have an in-built system to remove any misfolded protein. But when ribosomes cannot operate normally due to a mutation, defective ribosomal products build up and can place an unusually large burden on the cell’s protein degradation system – a phenomenon called proteotoxic stress.

This finding opens up promising avenues for future therapeutics. The scientists proposed that this proteotoxic stress can be relieved by boosting the removal of toxic waste from cells (a process called autophagy), as well as combining with treatments that enhance protein production quality. Similar interventions have already been considered for diseases that involve protein aggregates, such as Alzheimer’s disease and Huntington’s disease.

Disclaimer: This paper was performed in the author's current lab group, but they were not involved in the research.