Surprising discovery in yeast could open the door to new cancer treatments

The discovery of a surprising way yeast used to brew beer can survive starvation could open the door to new treatments for cancer.

The discovery by scientists at the University of Virginia School of Medicine and their collaborators at EMBL in Germany reveals an unprecedented adaptation that helps yeast cells go dormant when nutrients are scarce. This ability to hibernate when stressed reflects the cancer’s ability to survive nutrient shortages that accompany the uncontrolled growth of cancer cells.

The unexpected findings could lead to new strategies to make cancer cells more susceptible to starvation and easier to treat, said researcher Ahmad Jomaa, PhD, of the School of Medicine’s Department of Molecular Physiology and Biological Physics.

“Cells can take a break when things get tough by going into deep sleep to stay alive, and at a later point they just seem to come back,” said Jomaa, part of UVA’s Center for Membrane and Cell Physiology. “Therefore, we need to understand the fundamentals of adaptation to starvation and how these cells become dormant in order to stay alive and avoid death.”

Survive stress

S. pombe is a type of yeast that has been used to brew beer for centuries. But its similarity to human cells also makes it an invaluable research tool for scientists. Through better understanding S. pombewe can better understand basic cellular processes in both healthy and cancer cells.

Working with Simone Mattei, PhD, and colleagues at EMBL, Jomaa and his team discovered that when the yeast cells’ batteries go into hibernation to avoid stress, they wrap themselves in an unexpected blanket. The surfaces of these batteries, called mitochondria, are covered with deactivated ribosomes, cellular machines that normally make proteins.

It remains a mystery why these inactive ribosomes attach to mitochondria. “There could be different explanations,” Mattei said. “A starved cell eventually begins to digest itself, so the ribosomes may cover the mitochondria to protect them. They could also accumulate to trigger a signaling cascade within the mitochondria.”

Using amazingly powerful single-particle cryo-electron microscopy and cryo-electron tomography, the researchers were able to visualize how the ribosomes attach to the mitochondria down to the molecular level. They were surprised to find that the ribosomes had attached themselves “upside down” using a small subunit of their anatomy. This type of interaction has never been observed before and could help unravel the mystery of how cells enter and emerge from dormancy. “We knew that cells would try to conserve energy and turn off their ribosomes, but we did not expect that they would attach to mitochondria in a reversed state,” said Maciej Gluc, a graduate student in Jomaa’s lab and co-first author a new scientific paper describing the discovery.

The new findings could have important implications for our understanding of cancer. Due to their uncontrolled growth, cancer cells constantly suffer from a lack of nutrients and often go dormant in order to survive and avoid detection by our immune system. Understanding how they do this could lead to new ways to specifically target the cancer cells to improve patient outcomes and prevent relapses.

“For the next steps, we want to understand not only how cells regulate their entry into the resting state, but also how they wake up from this deep sleep. We’re going to use yeast for now because it’s much easier to manipulate. We are now also investigating this.” “Culturing cancer cells, which is not an easy task,” said Jomaa.

Ultimately, I hope that my group’s research will lay the foundation for the discovery of new markers to track dormant cancer cells. These cells are not easy to detect in diagnostics, but we hope our research will generate more interest and help us achieve our goal.”

Ahmad Jomaa, PhD, Researcher, Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine

Better understanding cancer and finding innovative treatments are the primary missions of the UVA Cancer Center, recognized by the National Cancer Institute as one of only 57 “comprehensive” cancer centers. The award recognizes cancer centers with the best cancer research and treatment programs in the country.

Results published

The researchers published their results in the journal Nature Communications. The research team consisted of Olivier Gemin, Gluc, Michael Purdy, Higor Rosa, Moritz Niemann, Yelena Peskova, Mattei and Jomaa. The scientists have no financial interest in the work.

The research was supported by the Searle Scholars Program, the American Cancer Society, UVA’s Department of Molecular Physiology and Biological Physics, and the European Molecular Biology Laboratory.