The new findings reveal the mystery of how cells deal with stress

As shown in the figure, the effect of the protease ClpX is shown: the gray part identifies harmful proteins, the orange part catches harmful proteins, and the blue part destroys harmful proteins
.

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 at the University of Massachusetts Amherst investigated the mystery
of how cells handle stress in a recent study published in the journal Cell Reports.
The researchers found that a damage repair enzyme called ClpX may not only mutate to repair a variety of cellular problems, but also respond to changes in cellular energy levels to maintain cell health
.

"What we're really interested in is how cells respond to stress," said
Peter Chien, senior author of the paper and professor of biochemistry and molecular biology at the University of Massachusetts Amherst.
We study a class of enzymes called proteases that target and destroy harmful proteins
inside cells.
These proteases can selectively recognize specific, individual proteins, single proteins
.
But how did they do it? How do they choose between healthy protein and harmful protein?"

To answer this question, Chien and his co-authors focused on two specific proteases, called Lon and ClpX, each finely tuned to recognize a different harmful protein
.
It has long been thought that Lon and ClpX function like keys: they can only open one lock, not another
.
If a cell lacks any of these locks, it can have serious side effects
.

"If you've ever had a really scruffy college roommate," Chien says, "you know how important it is to
take out the trash regularly.
" Losing Lon protease is like having a roommate
who never bathes, changes clothes, or cleans.
”

But in a series of experiments that removed Lon from bacterial cell colonies, Chien's team found something strange: Some colonies were still alive
.

This observation led to their first discovery: ClpX can mutate to perform functions similar to lon, although it loses some of ClpX's abilities
.
It's like when you start washing your roommate's socks in order to keep your dorm room clean, but you have to sacrifice some of your clean clothes
.

In precisely tracing how ClpX mutations allow proteases to expand their function, the team made a second discovery: Under the right conditions, wild non-mutant ClpX can also perform some of Lon's duties
.

ClpX has proven to be highly sensitive to ATP, an organic compound that is the energy source for
all living cells.
At normal ATP levels, ClpX focused on its duties, but at a specific, lower threshold, it suddenly began to clean up Lon after
that.

"This is a real breakthrough in the fundamental understanding of how cells work," Chien said
.
"It changes the rules: cellular energy not only controls how fast the cell works, but also how it works
.
"

Reference: ATP hydrolysis tunes specificity of a AAA+ protease