News

Research that shines light on how cells recover from threats

May lead to new insights into Alzheimer’s and ALS
Brian Andrew Maxwell
By Brian Andrew Maxwell
Aug. 21, 2021

Our bodies contain a special protein tag that plays a role in how cells recover from specific threats to their survival, according to new research I co-authored. Understanding how this process works may be key to future treatments for neurodegenerative diseases, such as Alzheimer’s disease and some forms of dementia.

Cells regularly encounter potentially harmful changes in their environment, such as fluctuating temperature or exposure to UV light or toxins. To ensure survival, cells have evolved complex ways to adapt to these stressful changes. These mechanisms range from temporary changes in metabolism to wholesale shutdown of critical biological processes that might otherwise be permanently damaged.

Cells-recover-445x219.jpg
Michael Hughes, CC BY-ND
Ubiquitin tags in cells serve different functions depending on stress conditions.

For example, many cellular stresses temporarily shut down protein production while messenger RNAs, which carry part of the DNA code through the cell, become sequestered in dense structures known as stress granules. When the stress passes, the stress granules are disassembled and cells emerge from this defensive state to resume normal activities.

But until now, molecular biologists like me didn’t understand exactly how this mechanism worked.

In a pair of peer-reviewed studies published in the journal Science on June 25, 2021, my colleagues and I working in J. Paul Taylor’s cell and molecular biology lab explain how a protein known as ubiquitin is responsible for getting cells back up and running once the coast is clear.

In the first study, I discovered that different types of stress lead to specific proteins in cells getting tagged with ubiquitin in distinct ways. I exposed cells to either heat stress or a toxic chemical, then blocked the ubiquitin-tagging process after seemingly identical stress granules formed. To my surprise, blocking ubiquitin tagging only prevented stress granule disassembly for heat shock. Importantly, I also found that cells were unable to restart key biological processes like protein production and transport when these stress granules remained present, even after a return to normal temperatures.

In the second study, my colleague Youngdae Gwon looked closer into this process. He discovered that heat stress triggers ubiquitin tagging of a key protein that allows an enzyme to disassemble stress granules. This enzyme grabs onto the ubiquitin tag and uses it as a handle to pull the structure apart.

Why it matters

Researchers have linked stress granule biology and the stress response process in general to several neurodegenerative diseases, including Alzheimer’s disease, ALS or Lou Gehrig’s disease, and some forms of dementia.

For example, mutations in the the same protein, which we found to be necessary to dissemble stress granules, can cause inherited neurodegenerative diseases. Understanding how stress granules are regulated is critical to getting a better grasp on how these diseases work and potentially finding new treatments for them.

Stress granules play a role in the development of neurodegenerative diseases like ALS.

What still isn’t known

Although we identified several key factors in the role ubiquitin plays in the disassembly of stress granules, many molecular details of this process remain unknown. To gain further insight, scientists will need to identify which enzymes are responsible for putting the ubiquitin tag on proteins during stress in the first place. Additionally, it will be important to understand how mutations that lead to neurodegenerative diseases might also affect the stress recovery process.

What other research is being done

Researchers are investigating various aspects of stress granule biology and its links to neurodegenerative disease. Some are working to recreate stress granules in a test tube to explore questions not easily answered by working in cells. And others are looking inside live neurons, mice and fruit flies to understand how disease mutations affect stress recovery in living cells and creatures.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

The Conversation

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition monthly.

Learn more
Brian Andrew Maxwell
Brian Andrew Maxwell

Brian Andrew Maxwell, Scientist in Cell Biology, St. Jude Children’s Research Hospital Graduate School of Biomedical Sciences

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Gaze into the proteomics crystal ball
In-person Conference

Gaze into the proteomics crystal ball

July 1, 2025

The 15th International Symposium on Proteomics in the Life Sciences symposium will be held August 17–21 in Cambridge, Massachusetts.

Bacterial enzyme catalyzes body odor compound formation
Journal News

Bacterial enzyme catalyzes body odor compound formation

June 27, 2025

Researchers identify a skin-resident Staphylococcus hominis dipeptidase involved in creating sulfur-containing secretions. Read more about this recent Journal of Biological Chemistry paper.

Neurobiology of stress and substance use
Profile

Neurobiology of stress and substance use

June 19, 2025

MOSAIC scholar and proud Latino, Bryan Cruz of Scripps Research Institute studies the neurochemical origins of PTSD-related alcohol use using a multidisciplinary approach.

Pesticide disrupts neuronal potentiation
Journal News

Pesticide disrupts neuronal potentiation

June 17, 2025

New research reveals how deltamethrin may disrupt brain development by altering the protein cargo of brain-derived extracellular vesicles. Read more about this recent Molecular & Cellular Proteomics article.

A look into the rice glycoproteome
Journal News

A look into the rice glycoproteome

June 17, 2025

Researchers mapped posttranslational modifications in Oryza sativa, revealing hundreds of alterations tied to key plant processes. Read more about this recent Molecular & Cellular Proteomics paper.

Proteomic variation in heart tissues
Journal News

Proteomic variation in heart tissues

June 17, 2025

By tracking protein changes in stem cell–derived heart cells, researchers from Cedars-Sinai uncovered surprising diversity — including a potential new cell type — that could reshape how we study and treat heart disease.