Study shows link between metabolic and cell division mechanisms

Several biological processes are subject to rhythmic variations. Popular examples of this include the supposed circadian rhythm—that is, an “internal clock” with a duration of about 24 hours—or the slightly shorter, ultradian rhythm. The division of cells is usually associated with this rhythm.

Professor Dr Bruce Morgan. Image Credit: Saarland University/Jörg Pütz.

Now, biologists have found that this rhythm as well as its coupling with cell division is closely associated with hydrogen peroxide (H₂O₂). The new study was published in the Nature Chemical Biology journal.

In living beings, the processes follow a well-organized choreography at the molecular level. Strictly prescribed rhythms are of major significance for these processes in the body and these rhythms are followed by specific cycles. For instance, the 24-hour circadian cycle, a sort of “internal clock”, plays a significant role in cell division and metabolic mechanisms in the cells.

Now, researchers from Saarbrücken and Kaiserslautern have closely looked at an analogous cycle, the slightly shorter ultradian cycle of baker’s yeast. The research team, under the guidance of Bruce Morgan, Professor of Biochemistry at Saarland University, wanted to find out what precisely occurs in the model organism of baker’s yeast when the cells’ metabolism is altered in a targeted way.

It was already known that the cell division cycles and the metabolic processes in healthy cells usually run synchronously and accurately according to such rhythms. But to date, it still remains an enigma whether rhythmic variations in metabolism are the consequence or cause of cell division.

Using new fluorescent sensors, the team was able to view the rhythmic changes in the H₂O₂ level. Historically, H₂O₂ was better known for damaging and stressing cells.

We also examined the protein peroxiredoxin and its reaction, as well as the effects on the cell division cycle of the cells. This is because the protein peroxiredoxin is very sensitive to hydrogen peroxide and is therefore particularly suitable for further understanding the complex mechanism of the cells' ‘internal clock.’”

Dr Bruce Morgan, Professor of Biochemistry, Saarland University

Now, the team was able to answer the query of whether this rhythmic change is the consequence or causes the metabolic change.

We were able to determine that the link between metabolism and cell division is broken when we inactivate the peroxiredoxin in baker’s yeast.”

Dr Bruce Morgan, Professor of Biochemistry, Saarland University

The researchers subsequently decoupled cell division from the cell metabolism. Additionally, they were able to accurately regulate when the cells penetrate and leave the cell division cycle by exactly regulating the metabolic cycles.

These underlying findings could be crucial for interpreting the uncontrolled division of cells in tumor cells. It is well known that cell division in tumor cells is usually decoupled from the circadian clock. In the days to come, it will be quite fascinating to study whether a disrupted H₂O₂ regulation is involved.