An unexpected observation of yeast paves the way for innovative methods in cancer diagnosis and treatment.

The discovery made by scientists from the University of Virginia School of Medicine and their colleagues from EMBL in Germany indicates an unprecedented adaptation that aids yeast cells in entering a dormant state during nutrient scarcity. This ability to hibernate under stress mirrors how cancer survives nutrient deprivation that accompanies uncontrolled cancer cell growth.

According to researcher Ahmad Jomaa, Ph.D., from the Department of Molecular Physiology and Biological Physics at the School of Medicine, the unexpected findings could lead to the development of new strategies to detect cancer cells and make them more vulnerable to starvation, thus easier to treat.

“In challenging situations, cells can take a break by entering a deep sleep to survive, and then they seemingly just return later,” says Jomaa. “That’s why we need to understand the fundamentals of starvation adaptation and how these cells transition into a dormant state to survive and avoid death.”

Collaborating with Simone Mattei, Ph.D., and colleagues from EMBL, Jomaa and his team discovered that when the "power stations" of yeast cells shut down and enter sleep mode to evade stress, they wrap themselves in an unexpected blanket. The surface of these "cellular power stations," known as mitochondria, becomes coated with deactivated ribosomes—cellular components that typically produce proteins.

The researchers were able to observe at the molecular level how ribosomes attach to mitochondria using extremely powerful single-particle cryo-electron microscopy and cryo-electron tomography. They were surprised to find that ribosomes attach "upside down." This type of interaction had never been observed before and may help decode the secret of how cells enter a dormant state and awaken from it. “We knew that cells try to conserve energy and fold their ribosomes, but we didn’t expect them to attach to mitochondria in an inverted position,” says the researcher.

The new findings could have significant implications for our understanding of cancer. Due to uncontrolled growth, cancer cells experience a constant shortage of nutrients, often entering a dormant state to survive and evade detection by the immune system. Understanding how they do this could lead to new ways to target cancer cells to improve patient outcomes and prevent relapses.

“In the next stages, we want to understand not only how cells regulate their entry into a dormant state but also how they awaken from this deep sleep. For now, we will use yeast because they are much easier to manage. We are also investigating this process in cultured cancer cells, which is a challenging task,” says Jomaa.

Ultimately, I hope that my group’s research will lay the groundwork for discovering new markers that allow us to track dormant cancer cells. These cells are difficult to detect during diagnosis, but we hope our study will generate greater interest and help us achieve our goal.

The researchers published their findings in the scientific journal Nature Communications.