Linking lipid metabolism changes to the stress response

Lipid homeostasis and optimal ER stress response.

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This study is about how cells handle fats and can impact how they react when stressed. Researchers want to understand how changes in fat processing affect how cells deal with stress.

A fresh study from University of Southern California and UC Berkeley researchers uncovers how fat processing shifts can affect cell health as they age and cope with stress.

The study investigates a part of cells known as the endoplasmic reticulum (ER), which makes proteins and fats essential bodily substances. 

This ER acts like a “cell factory,” ensuring proteins and fats are in good condition. Gilberto Garcia, a USC Leonard Davis School of Gerontology researcher, explains that a well-working ER is crucial to keeping proteins and fats healthy within cells.

Garcia and the team looked at a gene named let-767 in a worm called C. elegans. This gene has a significant role in keeping fats and proteins made by the ER in good shape. When they quieted the let-767 gene, the worms had less fat. The ER’s structure changed, affecting its ability to handle protein-related stress. These worms were smaller and had shorter lives as a result.

Ryo Sanabria, assistant professor of gerontology at the USC Leonard Davis School and a co-author of the study, said, “let-767 codes for an enzyme that gets rid of toxic lipids and then converts them into good lipids. So if you get rid of it, it destroys ER health in two ways: it accumulates the toxic product it’s supposed to get rid of, and you don’t have the good stuff it’s supposed to turn it into.”

When the let-767 gene was stopped, leading to a decrease in fats, the cells couldn’t trigger a process called the Unfolded Protein Response of the ER (UPRER). This process usually fixes improperly folded proteins. The inability to do this might be connected to diseases like Alzheimer’s, Parkinson’s, and others that involve abnormal proteins piling up.

According to Sanabria, who was part of the study, this discovery shows that changes in how fats work could make it hard for cells to handle protein issues, which could speed up diseases.

This study underscores the intricate relationship between changes in lipid metabolism and how cells respond to stress. It emphasizes the importance of maintaining lipid balance for effective stress response mechanisms. Future research could provide valuable insights for developing strategies that bolster cellular stress adaptation.

Journal Reference:

  1. Gilberto Garcia, Hanlin Zhang., Lipid homeostasis is essential for a maximal ER stress response. eLife. DOI: 10.7554/eLife.83884.