At certain gatherings, it is understood that each person will pick up their share of the tab, or some portion of it, at least. Now it appears that the idea of paying one’s own way isn’t just for lunch meetings and the like. It even reaches down to the subcellular scale, where the occasion is cell division, the partiers are subunits of a key protein complex, and the exchange of currency is represented by phosphorylation.
To be more precise, the occasion is the G2 phase of the cell cycle, during which cell division pauses after DNA replication to check for genetic damage. Once any damage has been repaired, the cell can move into mitosis and begin dividing.
The subcellular partiers are the proteins of the cyclin B1/Cdk1 complex, which has long been known to play a key role in cell division. This complex, it now appears, also boosts mitochondrial activity to help power the process.
And power is indeed required to keep the cell cycle going. Where this power comes from was unknown until researchers at UC Davis took a closer look at the mechanisms underlying the coordination of mitochondrial respiration with cell-cycle progression. These researchers found that a fraction of cyclin B1/Cdk1 proteins, in addition to participating in cell division, localizes to the matrix of the mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I subunits in the respiratory chain. By phosphorylating the complex I proteins, cyclinB1/Cdk1 essentially transfers energy to them, increasing the ability of mitochondria to produce ATP, which powers most cellular activities.
“These proteins not only control the cell cycle, but they also moonlight to increase mitochondrial energy,” said Jian Jian Li, M.D., Ph.D., professor of radiation oncology and director of Translational Research at the UC Davis Comprehensive Cancer Center. “They synchronize these processes because the cell cycle cannot proceed without the extra energy.”
Dr. Li and colleagues described their work in an article entitled “Cyclin B1/Cdk1 Coordinates Mitochondrial Respiration for Cell-Cycle G2/M Progression,” which appeared April 17 in the journal Developmental Cell.
The article includes details of how the researchers both mouse and human cells, including breast cancer cells and normal human breast epithelial cells, to assess how cyclin B1/Cdk1 controls mitochondrial energy metabolism during cell cycle G2/M progression. The researchers found that increased mitochondrial protein phosphorylation by the cyclin B1/Cdk1 complex boosted energy production, while reversing that process reduced energy.
This is the first evidence that cyclin B1/Cdk1 both senses the cell’s energy needs during the G2/M transition and communicates that information to mitochondria.
Given its key role in cellular energy production, cyclin B1/Cdk1 could be an attractive therapeutic target, particularly in cancer. “Like cars, tumors need a lot of gas,” said Dr. Li. “If we reduce the amount of gas, we could perhaps slow down the cancer.”
Besides suppressing tumor growth, it may be possible to enhance the effects of radiation and chemotherapy. According to Dr. Li, tumor cells under stress “may need mitochondria to provide extra energy to repair DNA damage”
“If we block this communication between nucleus and mitochondria in tumor cells and inhibit glycolysis, this could be a new approach to treating cancer,” concluded Dr. Li.