How cells balance their protein levels

Every cell depends on proteins to function and stay healthy. These proteins are made inside the cell from amino acids but cannot simply accumulate inside the cell forever. Once they have done their job or become damaged, the cell needs to clear them out.

Cells do this by breaking proteins down and recycling them, a process summarily referred to as “protein removal”. But this ongoing and vital "dance" of protein making and protein removal takes energy and coordination, and the cell must constantly strike the right balance between the two.

When resources such as amino acids or the cell’s capacity to build proteins fluctuate—e.g. after eating, during stress, or in the presence of certain drugs—this balance can shift. And yet, cells still need to keep their overall protein levels within a safe range.

This raises a simple question: how do cells adjust protein removal when protein production changes? Scientists have known the two processes, protein production and removal, are linked. What is missing is a clear, quantitative picture of how they move together in real time.

“Cells are constantly subjected to fluctuations in the resources that govern protein synthesis,” says Professor David Suter at EPFL’s School of Life Sciences. “If protein synthesis rates go down by 50%, our cells would shrink by 50% unless protein elimination rates slow down as well.”

Suter and his team have now mapped how mammalian cells coordinate protein production and removal. “We discovered a universal property of mammalian cells: their ability to partially adjust protein elimination rates to changes in protein synthesis rates, mostly through a mechanism we call Passive Adaptation.”

The research is published in Cell Systems.

Discovering Passive Adaptation

To study how cells handle changes in protein production, the researchers used a special fluorescent protein that changes color with time. This made it possible to track how quickly new proteins were made and how fast older ones were removed in single living cells.

By analyzing these color changes, the team measured two processes: active protein breakdown and the dilution of proteins as cells grow and divide. They then compared these measurements to a mathematical model that predicted that if protein production slows, the cell also makes fewer components of its degradation machinery, which in turn slows protein elimination.

Across all conditions tested, the data fit the model: when protein synthesis fell, protein elimination slowed just enough to partially compensate. This is what the scientists are calling “passive adaptation”, a process that helps cells maintain safer protein levels despite fluctuations in resources.

The same behavior appeared even in cells that were unperturbed by external factors, showing that this is a natural, everyday strategy.

Why embryonic stem cells behave differently

When the team examined mouse embryonic stem cells, they found an extra layer of protection. These cells activated a nutrient-sensing pathway called mTOR when protein synthesis dropped. This response increased protein-building capacity and further reduced protein breakdown, allowing the cells to keep their protein levels almost perfectly steady.

“Even if protein synthesis rates go down by 50%, they maintain almost perfectly constant protein levels,” says Suter.

He adds that this robustness likely matters in real embryos: “We think this might be needed for these cells that are part of the pre‑implantation embryo, where conditions are harsh with no blood supply and limited nutrients. It may also help explain the resilience of blastocysts [the hollow ball of cells 5-6 days after an egg is fertilized] in the simple culture conditions that were initially used in IVF.”

The work clarifies how cells protect their protein balance during changes in nutrient availability, development, or stress. It also offers insight into how scientists interpret protein‑stability measurements and how early embryonic cells maintain their resilience.

Reference

Michael Shoujie Sun, Benjamin Martin, Joanna Dembska, Ekaterina Lyublinskaya, Cédric Deluz, David M. Suter. Core passive and facultative mTOR-mediated mechanisms coordinate mammalian protein synthesis and decay. Cell Systems 22 December 2025. DOI: 10.1016/j.cels.2025.101456

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