Hibernation factor

A hibernation factor is a protein used by cells to induce a dormant state by slowing or halting the cellular metabolism. This can occur during periods of stress, randomly in order to allocate "designated survivors" in a population, or when bacteria cease growth (enter stationary phase). Hibernation factors can do a variety of things, including dismantling cellular machinery and halting gene expression, but the most important hibernation factors bind to the ribosome and halt protein production, which consumes a large fraction of the energy in a cell.



Ribosome hibernation
Ribosome hibernation occurs when ribosome hibernation factors bind to the ribosome and halt protein production. Ribosome hibernation is almost ubiquitous in bacteria, as well as in the plastids of plants, and may also be present in eukaryotes. Ribosome hibernation factors can simply inactivate ribosomes, (RaiA) link pairs into inactive dimers, like 100S ribosomes, (RMF and HPF) or interfere at various stages of the translation cycle (RsfS, YqjD, SRA, and EttA). One indicator of ribosome hibernation is the presence of a large number of 100S ribosomes, which can constitute up to 60% of the ribosomes in a cell at a times.

RMF, RaiA, and HPF
Three proteins, RMF, RaiA, and HPF, are only found in the large class of bacteria gammaproteobacteria. RMF (Ribosome modulation factor) is a small protein, typically produced under nutrient starvation and stress conditions, that is the main factor in the formation of 100S ribosomes. During the formation process, RMF binds together 70S (standard) ribosomes to form 90S ribosome dimers. These 90S dimers are converted by HPF (hibernation promoting factor) to form mature 100S dimers. A third protein, RaiA (ribosome-associated inhibitor A) is thought to both inactivate 70S ribosomes alone and stabilize them, preventing them from being converted into 100S ribosomes. Most non-gammaproteobacteria, as well as some plant plastids, instead contain a HPF homologue that can form 100S ribosomes by itself.

Balon
Balon (Spanish "ball", after homologue Pelota) is a hibernation factor protein found in the cold-adapted bacterium Psychrobacter urativorans. The protein was discovered accidentally by a researcher who unintentionally left a sample of P. urativorans in an ice bucket for too long, cold-shocking it, through subsequent cryo-EM scans of the organism's ribosomes. Unlike other factors, Balon can bind to the ribosome while protein production is in process. This is important for rapid response to stress because in some cells, protein production can take up to 20 minutes to complete. Balon does this by rather than physically blocking the A site of the ribosome, as other hibernation factors do, binding near to but not across the channel, allowing it to attach to the ribosome independent of whether protein production is taking place. Genetic relatives of Balon have been found in 20% of bacterial genomes catalogued in public databases, but are absent from Escherichia coli and Staphylococcus aureus, the most widely used models for cellular dormancy.