In a pair of publications, researchers have shown how cells adapt to stressors--like water loss--by reprogramming their internal signaling networks. The studies describe previously unknown mechanisms that cells use to send signals between cellular machinery and avoid cell death. According to the authors, drugs that enhance the adaptation mechanisms could help cells stave off multiple diseases, including type 2 diabetes. The studies were published in Cell Reports and Molecular Cell.
"We discovered that cells switch off non-essential functions when faced with threats to their survival. At the same time, cells activate new mechanisms to sustain essential functions," said senior author on both papers.
The studies focus on two types of cellular stress: cell shrinkage from water loss, and dysfunction of the endoplasmic reticulum, the cellular organelle that makes and guides proteins to specific destinations. Both have diverse causes--everything from a person's genetics to a cell's environment--and cells must adapt to the stressors, or perish. In the new studies, researchers describe a series of cellular workarounds. "Cells protect themselves by slowing down energy-consuming processes, such as protein synthesis. This prepares cells to reprogram the cellular machinery to make only the essential proteins needed for survival," senior author said.
In the Molecular Cell study, researchers describe how stressed cells focus on critical protein production to sustain the function of the endoplasmic reticulum, by transmitting signals along unexpected molecular pathways. In the Cell Reports study, researchers put cornea cells in salt water to dry them out. The cells responded by activating pathways that help transport amino acids. By doing so, the cells were able to prevent water loss. The findings suggest medications that target the transport pathways could help treat dry eye syndrome. Such medications may also help treat neurodegenerative diseases caused by defects in protein equilibriums.
The senior author said, "Both our papers contribute to our understandings of the ways cells try to ensure proteins are properly folded and navigated through the cells, so they can reach their final destinations and assume their normal functions. This process is known as the 'integrated stress response.'" In Molecular Cell, researchers outline how cells can "reprogram" the integrated stress response. As the journal explains, the authors "unravel the mechanism of adaptation to chronic stress that encompasses previously unappreciated remodeling." The study outlines a cascade of new cellular signals that cells use to adapt to stressful conditions. Interestingly, the novel stress defense mechanism involves remodeling of the cellular machinery that translates mRNA genetic material into a select group of proteins. This selective protein synthesis protects stressed cells from life-threatening endoplasmic reticulum dysfunction.
In Molecular Cell, researchers also show that endoplasmic reticulum dysfunction is marked by a novel cell death mechanism involving cytoplasmic vacuolization--the formation of large, toxic pockets inside cells that is reminiscent of foamy cells, observed in many human pathologies. This phenotype is a pathologic feature in the brains of the neurodegenerative diseases called childhood ataxias, and introduces the interesting possibility that their cause is the result of endoplasmic reticulum dysfunction in nerve cells.
The findings could also lead to new diabetes treatments. "Patients who develop type 2 diabetes become ill because they make too much insulin. This causes the endoplasmic reticulum to be overwhelmed and unable to handle the sudden protein overload, leading to dysfunction. This dysfunction later kills insulin-producing cells in the pancreas," said the senior author. "We believe by enhancing the adaptive response to increased insulin we can delay endoplasmic reticulum dysfunction and the onset of disease."
http://casemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=896
http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31647-9
http://www.cell.com/molecular-cell/fulltext/S1097-2765(17)30842-0
Cellular reprogramming during stress!
- 2,578 views
- Added
Edited
Latest News
How brains convert sounds t…
By newseditor
Posted 12 May
Mice with traits of Tourett…
By newseditor
Posted 11 May
Intermittent fasting protec…
By newseditor
Posted 11 May
Microfluidic systems resemb…
By newseditor
Posted 11 May
Neurotransmitter classifica…
By newseditor
Posted 11 May
Other Top Stories
Viruses such as SARS-CoV-2 can cause brain cells to fuse
Read more
How a parasite evades the immune system
Read more
New bacterial species involved in tooth decay
Read more
A small RNA that regulates bacterial infection discovered!
Read more
Herpes encephalitis infection in cerebral organoids
Read more
Protocols
Improved detection of DNA r…
By newseditor
Posted 09 May
Single-cell adhesive profil…
By newseditor
Posted 07 May
Parasympathetic neurons der…
By newseditor
Posted 07 May
Non-invasive measurements o…
By newseditor
Posted 05 May
A validation strategy to as…
By newseditor
Posted 04 May
Publications
Differential representation…
By newseditor
Posted 12 May
Glucose hypometabolism prom…
By newseditor
Posted 12 May
Organellophagy regulates ce…
By newseditor
Posted 12 May
Decoding mitochondria's rol…
By newseditor
Posted 11 May
APOE2 gene therapy reduces…
By newseditor
Posted 11 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar