NOV 15, 2016 05:55 PM PST

Ferroptosis - New Details on a Type of Cell Death

WRITTEN BY: Carmen Leitch
Researchers are still learning more about ferroptosis, a recently identified type of regulated cell death. It seems to be important to neuronal cell death after oxidative stress and is related to cancer. Iron appears to play a major role in the process, which is distinct from other types of cell death such as apoptosis and necroptosis. Only a few molecules that are involved have been identified. It is of note that labroots recently had a webinar related to ferroptosis featuring Brent Stockwell, watch that here.
 
A fibroblast undergoing ferroptosis. / Credit: Source: Helmholtz Zentrum München

A new publication from researchers at the Helmholtz Zentrum München demonstrates that a molecule involved in fatty acid metabolism, Acyl-CoA synthetase long-chain family member 4 (ACSL4), has a critical role in the initiation of this type of cell death. In collaboration with colleagues at the Universty of Pittsburgh, the investigators determined that the ferroptosis is triggered after a certain threshold of oxidized lipid molecules is reached in cellular membranes.
 
"Acsl4 is critically involved in shaping the cellular lipid composition by storing more poly-unsaturated long-chain fatty acids in cellular membranes, thereby providing the starting materials for the generation of the lethal lipid signals driving ferroptosis" explained doctoral student Sebastian Doll, first author of one of the two studies. "Previously it was assumed that iron-dependent lipid oxidation occurs randomly; however, our data now demonstrate that ACSL4 centrally contributes to the formation of oxidized lipid death signals in ferroptosis."
 
"The individual mechanisms involved in this type of cell death remain only partly understood, and our findings make an important contribution towards a better understanding of ferroptotic cell death," commented study leader Dr. Marcus Conrad, who leads a research group at the Institute of Developmental Genetics of the Helmholtz Zentrum München.
 
Cell death doesn’t conjure positive thoughts, but the destruction of specific, aberrant cells is very important to the health of the body, especially when it comes to cancer. In light of that, the researchers investigated the mechanism of ACSL4 in a cancer model. They found that a type of breast cancer cell that was not making ACSL4 was very resistant to ferroptosis, while if those cells were making ACSL4, they became highly sensitive to the induction of ferroptosis.
 
"This is a highly interesting finding given the fact that the presence of ACSL4 determines whether or not cells can embark on the ferroptosis pathway" explains Dr. José Pedro Friedmann Angeli, who was centrally involved in both studies. It is thus well conceivable, he says, that the molecule could be used as a biomarker in cancer patient stratification.
 
There were several findings reported in two research articles published in Nature Chemical Biology; the scientists also demonstrated a way to target ACSL4 in the ferroptotic signaling pathway. By using thiazolidinediones, a class of drugs that are frequently used to treat of diabetes, they were able to slow down the process of ferroptosis.
 
"Our intriguing insights that the ACSL4 enzyme plays a substantial role in the process of cell death provide novel cues for yet-unrecognized therapeutic approaches towards inhibiting ferroptosis in degenerative diseases or inducing ferroptosis in certain tumor diseases," said Conrad. The researchers say that tumors don’t respond to standard chemotherapy treatments could be good candidates for ferroptosis therapy. It is hoped that these findings will stimulate research in cancer and degenerative diseases.
 


For other molecular details of the ferroptosis process, watch the above video.
 
Sources: Nature, Cell, AAAS/Eurekalert! via Helmholtz Zentrum München, Nature Chemical Biology Doll et al, Nature Chemical Biology Kagan et al
 
About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
NOV 07, 2018
Cell & Molecular Biology
NOV 07, 2018
Lifespan Linked to Number of Cortical Neurons
Scientists linked the number of neurons in an organism's brain with the age of sexual maturity and lifespan of an organism....
NOV 19, 2018
Genetics & Genomics
NOV 19, 2018
Revealing an Unexpected Role for RNA in DNA Repair
When both strands of DNA break, it must be repaired or the cell will die....
NOV 24, 2018
Videos
NOV 24, 2018
Bats may Hold the Secret to Longevity
Some bats can live for up to 41 years, and many have a very healthy life....
NOV 25, 2018
Microbiology
NOV 25, 2018
Researchers Learn How Hantavirus Infects Cells
First identified in 1993, hantavirus infections can cause dangerous and potentially deadly respiratory infections....
NOV 26, 2018
Neuroscience
NOV 26, 2018
Behavior Predicting Neural Code Identified
Perceptual choice behavior, taking action based on the information received from the senses is often described by mathematical models...
DEC 13, 2018
Genetics & Genomics
DEC 13, 2018
Insights Into the Mechanisms Underlying Anxiety
Up to 40 million Americans have an anxiety disorder in any given year, and it's thought that only about a third get treatment....
Loading Comments...