New Findings Reveal How Cells Manage Stress – "Helping a Roommate Wash His Socks"

In a new study recently published in the journal, a team of scientists from the University of Massachusetts Amherst delve into the mysteries
of how cells resist stress.
By using bacterial cells, the researchers discovered a damage-repairing enzyme called ClpX, which not only mutates to repair multiple cellular problems, but also responds to changes in cellular energy levels to help keep cells healthy
.

"What we're really interested in is how cells respond to stress," said
Peter Chien, senior author of the paper and a 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
within 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 their attention on two specific proteases, called Lon and ClpX, each of which precisely recognizes a different harmful protein
.
It has long been thought that Lon and ClpX function like keys: each can only open one specific lock, not the others, and serious side effects
can occur if a cell lacks any of them.

"If you've ever had a very 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 cleanses.
”

But after conducting a series of experiments that included removing Lon from bacterial cell colonies, Chien's team began to notice something strange: Some colonies survived
.

This observation led to their first discovery: ClpX can mutate to perform Lon-like functions, although it loses some of ClpX's capabilities
.
It's like you start washing your roommate's socks to keep your dorm room clean, but have to sacrifice some of your own clean clothes
.

In precisely tracking how ClpX mutations allow proteases to expand their functions, the team made a second discovery: wild, non-mutated ClpX can perform some of Lon's duties
under the right conditions.

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 own duties, but at a specific, lower threshold, it also suddenly began to take on Lon's cleanup duties
.

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

ATP hydrolysis tunes specificity of a AAA+ protease