A misfolded protein helps yeast adapt to changing conditions

Proteins called prions are best known for causing a set of rare but fatal brain diseases, but not all prions are harmful. One newly identified prion helps yeast cells adapt to changing environmental conditions by controlling their growth and reproduction, reports a team co-led by UO biologist David Garcia.

Prions are misfolded versions of proteins that can spread to other cells and be passed on generation to generation. The protein that Garcia’s team studied is an enzyme called pseudouridine synthase, and it can take on two different shapes.

Yeast cells with the abnormal prion conformation reproduce more quickly, but also die sooner. With the usual conformation, they reproduce more slowly, but live longer, Garcia and his colleagues reported Sept. 21 in the journal eLife.

“We found some pretty dramatic changes in the growth of the cells and in the shortened lifespan,” Garcia said.

It’s not the first example of a tradeoff between reproductive rate and longevity. But this one is unique because the prion works by altering the way genes are turned on and off. So rather than being fated at birth to grow and reproduce quickly or slowly, yeast could adapt quickly based on the current environmental conditions.

Given a sudden influx of food, growth might speed up. During times of resource scarcity, yeast could hold off on growth and reproduction until conditions improved.

“Because these life states are reversible, our prediction is that yeast could fluctuate between them,” Garcia said.

Garcia did most of this research during his time as a postdoctoral fellow at Stanford University School of Medicine, working in the lab of Daniel Jarosz. Now, in his lab at the UO, Garcia plans to investigate whether similar mechanisms are at play in the world beyond yeast. The pseudouridine synthase enzyme is found in some form in many other species, including humans, but it isn’t yet known whether there’s a related prion that similarly affects cell growth.

“This work shows us that life can adapt fairly quickly in order to optimize its fitness,” Garcia said. “Even the smallest changes can really benefit organisms, and this is a case where we're not talking about small changes.”