Sleeping ribosomes reveal how stressed cells age
Every cell needs ribosomes to make proteins. But under stress, those ribosomes enter a kind of sleep mode. New research now shows in detail how that works, and what it means for ageing cells.
Ribosomes are the molecular machines in cells that produce proteins. When a cell is under pressure, many ribosomes stop working, entering a state called hibernation. Using an advanced microscopy technique (cryo-electron microscopy of cell extracts), researchers have for the first time mapped in detail which proteins cover and protect inactive ribosomes. The study appeared in eLife.
eEF2 as the main hibernation factor
The protein eEF2 (elongation factor 2) turned out to be bound to more than 95 per cent of sleeping ribosomes. That was unexpected: eEF2 was previously known only as part of active protein synthesis, not as a protector of hibernating ribosomes. Sleeping ribosomes also carried a wide range of other proteins, including factors involved in the mTOR signalling pathway (a network that regulates cell growth and ageing).
This is relevant for ageing because protein quality control (proteostasis) declines with age. Cells become less effective at producing the right proteins at the right time. If ribosomes become stuck in an incorrect sleep state, that could disrupt protein synthesis and contribute to cellular dysfunction.
A new method as the key
The researchers used a novel approach: studying cell extracts rather than purified molecules. This preserved the complexity of the cell environment more faithfully. Resolution was high enough to observe molecular interactions at near-atomic level. Whether the findings are directly applicable to human ageing has not yet been investigated.
Search terms to explore further: ribosome hibernation stress response cells, protein synthesis proteostasis ageing, mTOR signalling pathway ribosome regulation