Like a city, these structures require a great deal of resources to build and operate, and when resources are scarce, internal components must be recycled to provide essential building blocks, particularly amino acids, to sustain vital functions.
But how do cells decide what to recycle when they are starving? One prevailing hypothesis suggests that starving cells prefer to recycle ribosomes—cellular protein-production factories rich in important amino acids and nucleotides—through autophagy, a process that degrades proteins in bulk.
they systematically surveyed the entire protein landscape of normal and nutrient-deprived cells to identify which proteins and organelles are degraded by autophagy.
The analyses revealed that, in contrast to expectations, ribosomes are not preferentially recycled through autophagy, but rather a small number of other organelles, particularly parts of the endoplasmic reticulum, are degraded. Protein turnover is a constant and universal occurrence inside every cell. To recycle unneeded or misfolded proteins, remove damaged organelles, and carry out other internal housekeeping tasks, cells utilize two primary tools, autophagy and the ubiquitin-proteasome system.
Autophagy, derived from Greek words meaning "self-eating," allows cells to degrade proteins in bulk, as well as larger cellular structures, by engulfing them in bubble-like structures and transporting them to the cell's waste disposal organelle, called the lysosome.
In contrast, the proteasome pathway allows cells to break down individual proteins by tagging them with a marker known as ubiquitin. Ubiquitin-modified proteins are then recognized by the proteasome and degraded.
Previous studies in yeast have suggested that nutrient-starved cells use autophagy to specifically recycle ribosomes, which are abundant and a reservoir of key amino acids and nucleotides. However, cells have many other mechanisms to regulate ribosome levels, and how they do so when nutrients are low has not been fully understood.
One of the first analyses they carried out revealed that, in starving cells, total ribosomal protein levels decrease only slightly relative to other protein levels. This reduction appeared to be independent of autophagy. Cells that lacked the capacity for autophagy had no obvious defects when nutrient deprived.
Critically, the authors said, the results demonstrate that proteasome-dependent turnover of ribosomes likely contributes to a much greater extent than autophagy during nutrient stress.
the results demonstrate that proteasome-dependent turnover of ribosomes likely contributes to a much greater extent than autophagy during nutrient stress.
reference
Heeseon An et al, Systematic quantitative analysis of ribosome inventory during nutrient stress, Nature (2020). DOI: 10.1038/s41586-020-2446-y