University of Michigan researchers have found the first-ever early protection mechanism for cells under stress, reacting faster than the conventional gene expression pathways already known.

Using baker’s yeast for the study allowed researchers to ask open-ended questions, since fundamental pathways in yeast have thus far been homologous to those in animal cells. Yeast is often used to study cellular biology for its simple structure.

Natsuko Jin, a researcher with the Life Sciences Institute and the first author of the study, explained the role of the newly-discovered mechanism in a press release, saying it was “like a first responder rushing to an alarm while the larger response team mobilizes.”

The research findings, published in The Journal of Cell Biology, showed this first responder pathway helps yeast cells adapt to stress. In this study, specifically, cells under stress are those exposed to an environment of high salt concentration, called “high osmolarity.” The key role player in this early protection pathway is the production of lipid PI3,5P2, which increases within five minutes of salt exposure.

The findings encompass eight years of research at the University Life Science Institute. Though it has been long-known in the field that PI3,5P2 spikes in response to stress, Jin pursued research of this realm because prior to this study, the physiological role of PI3,5P2 was unknown. Her mentors encouraged her to explore the lipid and its biological implications. Though the study used yeast, Jin said its findings could apply to many other species.

“Since many of key players in this early protection pathway have been conserved through humans, other mammals, plants and yeasts, this indicates that this and other types of early protection pathways may exist more broadly and may respond to different types of cellular stress in many species,” Jin said.

Researchers went on to test what would happen if Fab1p, an enzyme that synthesizes PI3,5P2, was removed. They found over 80 percent of the yeast was dead in the high salt environment without Fab1p. On the other hand, when researchers removed the slower response pathway, only 30 percent died, demonstrating just how critical the newly discovered-pathway is to cell preservation. 

LSA junior Susan Wager, a cellular and molecular biology major, found the study to be fascinating. As pre-med student, Wager was intrigued by the possible implications these findings have on the cells of animals, including humans.  

“I would be interested to see if these findings can be replicated on more complex cells,” Wager said. “If there is a first responder mechanism in human cells, imagine all the cell damage that could be prevented. This is potentially revolutionary in science research.”

Researchers found kinases Pho85p and corresponding cyclin Pho80p do not make signaling lipid PI3,5P2, regardless of if the environment was of normal or high osmolarity. Rather, the findings showed, in high osmolarity, Pho85p phosphorylates Fab1p, which then goes on to synthesize PI3,5P2. Hence, Fab1p proves to be a major role player in this first responder pathway.

A similar rapid-response process also happens in the cells of mammals, prior to the conventional, long term pathway responding to high salt cell stress. Life Sciences Prof. Lois Weisman, the study’s third author, found this promising for more complex forms of life.

“Even in our own bodies, where our cells are more protected because we have all these different kinds of physiological regulations, we also experience stress,” Weisman said. “It interests me that that all along I believed, just like everyone else, that there was this relatively long-term protection mechanism … and what we found is that there’s actually this early protection mechanism.”

As for the future for the Weisman lab, researchers will look at neurons to see if there is a similar first responder pathway present, homologous to yeast cells.

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