Oxygen sensor in cells also controls cell division accuracy
Cells continuously measure how much oxygen is available. That turns out to matter not just during oxygen shortage, but also for something more routine: how cells divide.
Enzymes that sense oxygen, called prolyl hydroxylases (PHDs), are best known for regulating the cellular response to low oxygen. But the study in eLife shows that one specific enzyme, PHD1, also plays a role in orderly cell division. PHD1 modifies a protein called RepoMan that helps coordinate the division process. By adding a small chemical change, hydroxylation of proline at position 604, PHD1 influences how accurately cell division proceeds.
When that modification is absent, chromosomes fail to align properly and cells make more errors when distributing their genetic material. Cell death increases. While this sounds technical, it concerns a fundamental quality-control mechanism in every dividing cell in the body.
What this means for aging
Errors in cell division accumulate as we age. Cells that fail to distribute chromosomes correctly become a source of genetic instability. That instability is associated with aging and diseases such as cancer. The discovery that PHD1, through hydroxylation (the addition of an oxygen atom to an amino acid), influences the accuracy of cell division adds a new layer to our understanding of how oxygen sensing in cells may affect long-term health.
The study also reveals a link to the phosphorylation pattern of histone H3, a protein that packages DNA. The correct addition and removal of chemical groups on this protein is necessary for accurate chromosome segregation. PHD1 appears to help oversee this process through the RepoMan protein.
Fundamental, but telling
This is fundamental cell biology research. Direct clinical applications do not yet exist. Nevertheless, the insight that a cellular oxygen sensor also determines the quality of cell division is potentially relevant for anyone thinking about long-term cellular health. The researchers suggest that PHD1 activity coordinates a broader network of cellular processes than previously thought.
Search terms: prolyl hydroxylation cell division chromosome stability | PHD1 enzyme mitosis quality control | histone H3 phosphorylation chromosome segregation