Scientists have uncovered a fascinating new way yeast cells adapt to starvation, where ribosomes attach themselves to the mitochondria in a peculiar ‘upside-down’ manner. This finding could enhance our comprehension of how cancer cells manage to endure nutrient deficits.
What can we learn from stressed yeast about essential cellular processes? Quite a bit, as highlighted by researchers at the European Molecular Biology Laboratory (EMBL). Their studies include exploring how cells respond to stress, such as a lack of nutrients. One of their primary research subjects is the yeast species S. pombe, which has been used in traditional brewing for centuries. Being a eukaryote, this yeast shares several characteristics with human cells, making it a valuable model organism for studying core cellular functions.
Ribosomes flip upside-down in starving cells
Researchers have noted an extraordinary adaptation in yeast cells when they face starvation: their mitochondria are enveloped by large complexes known as ribosomes. Curious about this unusual behavior, the Mattei Team at EMBL Heidelberg and the Jomaa Lab at the University of Virginia School of Medicine conducted a deeper investigation using single-particle cryo-electron microscopy and cryo-electron tomography techniques.
Ribosomes serve as the cell’s heavy-duty molecular machines responsible for synthesizing proteins. Interestingly, in starving yeast cells, the ribosomes that gather on the mitochondria’s surface are not actively producing proteins. Instead, they are in a state of hibernation.
“To survive tough conditions until circumstances improve, a cell might minimize its energy consumption,” explained Olivier Gemin, EIPOD Postdoctoral Fellow in the Mattei Team, who led this study. “Protein synthesis requires significant energy, which can be conserved by putting ribosomes in a dormant state.”
The reason these hibernating ribosomes cling to the mitochondria remains a mystery.
“There may be various reasons,” suggested Team Leader Simone Mattei. “A cell under starvation might begin to break itself down, so the ribosomes could be there to shield the mitochondria. They might also be attaching to instigate a signaling process within the mitochondria.”
Mattei is also examining the notion that starving cells require a rapid energy production mechanism once food (glucose) becomes available again. Since mitochondria are the cell’s powerhouses, having ribosomes close by could facilitate the necessary protein production for energy generation.
What astonished the scientists was the discovery that ribosomes connect to the mitochondrial outer membrane in a manner that contradicts previous knowledge.
“Previously, it was known that ribosomes interacted with membranes only through their large subunit. However, in starving cells, we observed that they attach upside-down via the small subunit!” Mattei noted.
In upcoming research, the team aims to further explore the unique way these ribosomes attach.
Cancer cells endure their own challenges
The difficulties faced by starving yeast cells bear some resemblance to those endured by cancer cells.
Surprisingly, being a cancer cell is extremely challenging. When a tumor becomes aggressive, its cells proliferate rapidly, leading to a demand for nutrients and oxygen that exceeds availability. Consequently, many cancer cells find themselves in a state of continual starvation—a hell of their own making.
Nonetheless, they manage to survive and even proliferate.
“This is why it’s crucial for us to comprehend the fundamentals of starvation adaptation and how these cells remain dormant to survive and avoid death,” stated Ahmad Jomaa, Assistant Professor and Group Leader at the University of Virginia’s School of Medicine, and a senior co-author of the study. “We start with yeast because it is much easier to manipulate. Beyond this, we also try to deprive cultured cancer cells of nutrients, which is a challenging task, to learn how these cells withstand starvation and can sometimes lead to cancer recurrence.”
Gaining insight into these adaptive principles could help us devise strategies to counteract them, making cancer cells more vulnerable to starvation and therefore more responsive to treatment.
