A new protein is discovered in yeast

Researchers at the University of Arizona have discovered a protein that can be used to produce life-saving antifungal drugs
.
Yeast is everywhere, both inside and around our bodies, just like
bacteria.
Like bacteria, yeast can infect you and make you sick
.
About 150 million people are infected with yeast every year, and about 1.
7 million people die as a result, mainly
immunocompromised.

Yeast cells and human immune system cells use very similar chemical reactions to choose when to grow
.
Researchers at the University of Arizona have found tiny differences between the two cell types, which may promote the production of antifungal drugs that target disease-causing yeast in the body while protecting the immune system
.

Their research, published in the journal eLife, not only has implications for drug development, but also sheds light on how an ancient growth control pathway present in all multicellular organisms
has evolved over time.

The scientific community is well aware that a protein complex called TORC1 — short for rapamycin kinase complex 1 target — regulates the growth
of all cells from humans to yeast.
However, the protein that initiates this process in yeast was recently discovered and named Ait1
.
It is a nutrition sensor and TORC1 regulator
.
When functioning normally, Ait1 shuts down TORC1 when yeast cells lack nutrients, inhibiting cell growth
.
        

Andrew Capaldi, associate professor in the Department of Molecular and Cell Biology at the University of Arizona, member of the BIO5 Institute and co-author of the study, said: "Ait1 is a bit like a hand holding TORC1, reaching up with one finger to turn TORC1
on or off depending on how much nutrient is in the cell.
"

The Capaldi lab is interested in determining how cells sense stress and hunger and then decide how fast
they grow.
Understanding how TORC1 is triggered in different organisms is important
for developing treatments for a variety of diseases.

TORC1 was originally found in yeast, but it is also essential
for activating cells in the body's immune system to create a response.
When TORC1 does not work properly, it can trigger cancer, diabetes, and various neurological disorders, including epilepsy and depression
.

"If TORC1 is too active, it can cause cancer or epilepsy
.
If it's not active enough, it can lead to depression," Capaldi said
.
"We call it blonde supervision
.
"         

But the fact that the human body relies on the same TORC1 pathway as yeast poses a problem
.

Capaldi said that if scientists develop drugs that inhibit the growth of disease-causing yeast by controlling TORC1, "we will be in big trouble because TORC1 also controls the growth
of human immune cells and so on.
" ”

"For example, you can easily stop yeast growth with rapamycin, a drug that binds directly to and inhibits TORC1, so you can fight any infection
well," Capaldi said.
"However, transplant patients often use the same drugs to suppress their immune systems, so it would be a disaster
.
"

The researchers found that while the TORC1 pathway is very similar in yeast and humans, humans do not rely on Ait1 to regulate TORC1
.
Therefore, drugs specifically targeting Ait1 should inhibit the growth of yeast, not the growth
of human immune cells.

AIT1 has only evolved in the last 200 million years, which is relatively recent in terms of
evolution.
About 200 million years ago, a TORC1 regulator called Rheb seemed to disappear from the cells of various organisms, and that's exactly when
Ait1 evolved.

"We found that some of the ancient TORC1 regulators found in humans, including Rheb, were lost in yeast that obtained ait12 200 million years ago
," Capaldi said.
"Over the course of the evolution of other single-celled organisms, including many parasites and plants, these ancient regulators also disappeared
.
As a result, it is likely that other single-celled organisms have acquired new regulators—similar to Ait1—of their own
.
Now people can go out and look for them because they will also be good drug targets
.
”

Reference: "Ait1 regulates TORC1 signaling and localization in budding yeast" by Ryan L.
Wallace, Eric Lu, Xiangxia Luo and Andrew P.
Capaldi, 1 September 2022, eLife.