Slower Protein Breakdown Helps Explain Why Humans Develop More Slowly Than Mice

Researchers from the Ebisuya Group at EMBL Barcelona and PoL-TU Dresden, working with the Savitski Team at EMBL Heidelberg, measured protein degradation — the process of breaking proteins down into amino acids for recycling — across about 4,000 proteins shared between humans and mice. The findings, published in Developmental Cell, found a clear overall tendency for these proteins to be broken down more slowly in human cells than in mouse cells, even though not every protein followed the pattern.

The work built on earlier findings from the same group showing that HES7, a gene involved in embryo development, produces a protein that breaks down more slowly in human cells than in mouse cells, contributing to the slower pace of the human "segmentation clock" — the biological timer that governs how embryo body segments form. The new study asked whether this difference extends beyond a single protein.

The slower degradation was not limited to particular protein types or cell compartments, and appeared whether proteins were broken down via the proteasome or the lysosome — two different cellular disposal systems. "Instead, we discovered that slower protein degradation in humans is a general feature across the proteome," said Miki Ebisuya, group leader at PoL-TU Dresden and senior author.

To test what drives the difference, the researchers reduced metabolic activity in mouse cells, which slowed the cells' protein degradation and shifted their degradation rate and developmental speed to resemble that of human cells.