DEC 20, 2016 6:13 PM PST

New Research May Change Accepted View of Cell Cycle Control

WRITTEN BY: Carmen Leitch

The cells of organisms move through growth stages, duplicating DNA and eventually dividing, and control of that cycle was thought to be understood. The 2001 Nobel Prize in Physiology or Medicine was awarded for the demonstration that the cyclin-dependent kinase complex regulates the cell cycle. New work however, has followed up on some of the unexplained questions remaining in cell cycle control; researchers have discovered that a metabolic oscillator acts as the conductor of cell division. 

A very simple look at the cell cycle, from Wikimedia Commons

Some data has stood at odds with the accepted view; cells can divide in the absence of the cyclin machinery, for one. For another, in cells where the cycle is arrested, proteins of the late cell-cycle keep on oscillating. "But there were signs that [we didn't have] the complete story," said University of Groningen system biologist Matthias Heinemann. "We knew that metabolism often oscillated in synchrony with the cell cycle. So maybe, this was an autonomous control mechanism."

Heinemann looked at yeast cells growing in microfluidic channels so individual cells could be observed under a microscope for several days. The addition of fluorescent markers enabled the measurement of metabolic markers NADH, an electron carrier, and ATP, an energy source. From that, changes in the levels of those molecules that indicated clear oscillations were seen, usually moving along with the cell cycle. Heinemann added, "But we also noticed that occasionally cells did not divide, and that these cells still showed metabolic oscillations."

Molecular Cell 2016 Papagiannakis et al

Metabolism appeared to be oscillating independently of the cell cycle; well fed cells had rapid oscillations, poorly fed cells oscillated slowly. "We argue that metabolism and the cyclin-dependent kinase complex are coupled oscillators, which together orchestrate the growth and division of eukaryotic cells, but when metabolism is slowed down or sped up too much, the cell cycle can't keep up and stops," said Heinemann. The cyclin-dependent kinase complex moves to the rhythm of the metabolic oscillations, until it can't keep up. The graphical abstract from their work, published in Molecular Cell, is shown above.

The researchers suggest a system where the metabolic oscillations push the cyclin-dependent kinase complex through the cycle, controlling the timing of the various cell cycle stages. This new work could change a lot of textbooks. 

"The current view is too narrow and cannot explain why cells still divide when part of the cyclin-dependent kinase complex is removed," commented Heinemann. It is logical that evolution would favor a focus on the workings of metabolism.  "You would expect the earliest cells or proto-cells to have a simple control system to regulate division, and metabolism would be the obvious candidate." This new work could influence clinical research as well. "Most tumor cells have a very high metabolism. Interfering with metabolic processes could be a way to stop them from proliferating."

If you'd like to know more about gene oscillation networks, watch the following MIT lecture.

 

Sources: Science Daily via University of Groningen, NatureMolecular Cell

About the Author
BS
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
OCT 10, 2022
Cell & Molecular Biology
How STR Analysis Supports CAR-T Cell Manufacturing
OCT 10, 2022
How STR Analysis Supports CAR-T Cell Manufacturing
Engineered T cell therapies involve the genetic modification of a patient’s own immune cells with chimeric antigen ...
SEP 28, 2022
Genetics & Genomics
Microprotein Mutations May Significantly Increase Alzheimer's Risk
SEP 28, 2022
Microprotein Mutations May Significantly Increase Alzheimer's Risk
The mitochondrion, commonly called the powerhouse of the cell, might be one of the best known organelles. This special o ...
OCT 13, 2022
Immunology
SARS-CoV-2 Can Infect Fat Cells, Promoting Infection & Inflammation
OCT 13, 2022
SARS-CoV-2 Can Infect Fat Cells, Promoting Infection & Inflammation
SARS-CoV-2, the virus that causes COVID-19, is generally known to infect cells in the nose and respiratory tract by latc ...
NOV 02, 2022
Genetics & Genomics
A Mildly Pathogenic Mutation, Inherited Over 800 Years, Traces Back to One Person
NOV 02, 2022
A Mildly Pathogenic Mutation, Inherited Over 800 Years, Traces Back to One Person
Scientists have recently identified a genetic mutation that causes epilepsy, and carried by at least 90 people. These mu ...
NOV 23, 2022
Genetics & Genomics
How Mutant Mitochondrial DNA is Removed
NOV 23, 2022
How Mutant Mitochondrial DNA is Removed
Mitochondria are very special organelles. These cellular powerhouses do more than generate energy. They are known to car ...
NOV 28, 2022
Neuroscience
Experimental Drug Halts Deadly Brain Cancer Growth Without Harming Brain Cells
NOV 28, 2022
Experimental Drug Halts Deadly Brain Cancer Growth Without Harming Brain Cells
  Researchers have found that blocking a certain enzyme halts the growth of a childhood brain cancer tumor. The cor ...
Loading Comments...