In recent work that was published in the journal Cell Reports, a team of researchers from the University of Massachusetts Amherst investigated the mysteries surrounding how cells handle stress. Researchers found that an enzyme called ClpX can not only change to fix different problems in cells, but it can also respond to changing levels of energy in cells to keep them healthy.
“How cells react to stress is what we’re really interested in,” says Peter Chien, a professor of biochemistry and molecular biology at UMass Amherst and the paper’s senior author. We are researching a group of enzymes known as proteases that hunt down and eliminate harmful proteins inside of cells. These proteases have the ability to selectively identify particular, unique proteins. Yet, how do they accomplish this? How are they supposed to distinguish between beneficial and harmful proteins? ”
Chien and his co-authors focused on two distinct proteases, called Lon and ClpX, each of which is expertly tuned to recognize a different harmful protein, to address this question. Long believed to act as locks, Lon and ClpX could only open one type of lock at a time, and if either were missing from a cell, negative side effects would result.
“If you’ve ever shared a dorm with a particularly messy college roommate, you know how crucial it is to empty the trash frequently,” claims Chien. “Missing the Lon protease is equivalent to living with a house guest who never does the laundry, dishes, or cleaning.”
But after a series of tests in which Lon was removed from bacterial cell colonies, Chien’s team noticed something strange: some of the colonies were still existing.
They made their first discovery as a result of this observation: ClpX can mutate to carry out a Lon-like function, though it loses some of its ClpX characteristics. It’s as if you started washing your roommate’s socks in order to keep your dorm tidy, but you had to give up some of your own clean clothes in the process.
The team’s second finding was that, under the right circumstances, wild, non-mutant ClpX can also carry out some of Lon’s responsibilities. This was found while scientists were trying to figure out exactly how the ClpX mutation allowed the protease to do more.
As it turns out, ClpX is very sensitive to ATP, the organic compound that all living cells use as their energy source. ClpX concentrates on its own responsibilities when ATP levels are normal, but at a particular lower threshold, it starts abruptly cleaning up after Lon.
According to Chien, “This is a real breakthrough in the fundamental understanding of how cells work.” It changes the rules so that now the way a cell works is also controlled by its energy.
The National Institutes of Health, the Howard Hughes Medical Institute, the Institute for Applied Life Sciences at UMass Amherst, and the UMass NIH Chemistry Biology Interface Training Program all provided funding for this study. IALS brings together the deep and varied knowledge of 29 UMass Amherst departments to turn basic research into innovations that improve people’s health and well-being.
