researchers also found that reducing ATP levels enhances the degradation of certain substrates mediated by ClpXP, a damage repair enzyme.
According to a recent study by the University of Massachusetts Amherst, a specific enzyme may play a dual role in cellular health.
A team of researchers from the University of Massachusetts Amherst investigated the mysteries surrounding how cells handle stress in a recent study published in the journal Cell Reports . The researchers found that a damage repair enzyme called ClpX can not only mutate to solve multiple cell problems, but also respond to changes in cell energy levels to maintain cell health.
"What we are really interested in is," Peter, professor of biochemistry and molecular biology at the University of Massachusetts Amherst and senior author of the paper Chien said, "It's the cell's response to stress. We're studying a class of enzymes called protease , which target and destroy harmful proteins in cells. These proteases can selectively recognize a single protein of a specific, single protein. But how do they do it? How do they choose between healthy and harmful proteins? Rendering of
protease ClpX: The gray part recognizes harmful proteins, orange catches it, blue destroys it. Image source: Qian Lab
Chien and his co-authors focus on two specific proteases, called Lon and ClpX, each of which is finely tuned to identify different harmful proteins to answer the question. It has long been thought that Lon and ClpX function similarly to the key: each can only open one lock, not another, and if the cell lacks any one lock, it can cause serious side effects.
"If you ever had a very messy college roommate," Chien said, "you know how important it is to clear the garbage regularly. Missing Lon protease is like having a roommate who never washes, replaces or cleanses.
But after a series of experiments, Lon removed from the bacterial cell colony, Chien's team saw something strange: some colonies are still alive.
Peter Qian (right) and UMass undergraduate researcher Oluwabusolla Oliophie (left) conducted experiments in Chin's laboratory. Image source: UMass Amherst
This observation led to their first discovery: ClpX can be mutated to perform Lon-like functions, although it loses some of its ClpX capabilities. It's like, to keep the dorm clean, you start washing your roommate's socks, but have to sacrifice some of your own clean clothes to do so.
In the process of accurately tracking how ClpX mutations allow proteases to expand their function, the team made a second discovery: wild, non-mutant ClpX can also perform some of Lon's responsibilities under appropriate conditions.
It turns out that ClpX is highly sensitive to ATP, an organic compound that is the energy source of all living cells . At normal ATP levels, ClpX focuses on its own responsibilities, but at a specific lower threshold, it suddenly starts to clean up after Lon.
"This is a real breakthrough in the basic understanding of how cells work," Chien said. "It changes the rules: Cell energy not only controls how fast the cell works, but also how it works.
