Researchers uncover mystery of how cells handle stress
“What we’re really interested in,” said Peter Chien, professor of biochemistry and molecular biology at UMass Amherst University and senior author of the paper, “is how cells respond to stress. We study a class of enzymes called proteases, which Targets and destroys harmful proteins within cells. These proteases can selectively recognize specific, individual protein monomer proteins. But how do they do this? How do they choose between healthy and harmful proteins ?”
Chien and his co-authors focused on two specific proteases — Lon and ClpX, each of which is finely tuned to recognize different harmful proteins to answer this question. Lon and ClpX have long been thought to function like keys: each can only open one kind of lock, not the other, and if a cell lacks one, it can have serious side effects.
“If you’ve ever had an extremely messy college roommate,” Chien said, “you know how important it is to regularly empty the trash. Lack of Lon protease is like having a roommate that never washes, doesn’t change, doesn’t clean.”
But after a series of experiments that removed Lon from bacterial cell populations, Chien’s team saw something odd: Some colonies were still alive.
This observation led to their first discovery. Although it loses some of ClpX’s abilities, ClpX can be mutated to perform Lon-like functions. It’s like starting to wash your roommate’s socks in order to keep the dorm room clean, but having to sacrifice some of your own clean clothes to do so.
In tracing how mutations in ClpX allowed the protease to expand its function, the team made a second discovery: Under the right conditions, wild, non-mutated ClpX could also perform some of Lon’s duties.
It turns out that ClpX is highly sensitive to ATP. ATP is an organic compound that is the source of energy for all living cells. At normal levels of ATP, ClpX is focused on its duties, but at a certain, lower threshold, it suddenly starts cleaning up for Lon.
“This is a real breakthrough in the fundamental understanding of how cells work,” Chien said. “It changes the game: not only does cellular energy control how fast a cell works, but also how it works.”