Study reveals how neurons protect themselves from lipids damaged by oxidative stress

Controlling lipid transport in the brain is important as defects in lipid homeostasis contribute to neurodegenerative diseases. During oxidative stress neurons release lipids that are taken up by glia cells. This process plays an important role in protecting the brain as failure to transfer lipids to glia results in neurodegeneration. However, the mechanisms of lipid release from neurons and its consequences are poorly characterized. An exciting new study by Isha Ralhan and colleagues from University of Alberta, published in the Journal of Cell Biology, reveals a novel mechanism of lipid release from neurons during cellular stress. 

Using state-of-the art microscopy and biochemical assays, the researchers discovered that neurons release lipids damaged by oxidative stress by a process called autolysosomal exocytosis. Failure to release these lipids causes peroxidated lipids and iron to accumulate, sensitizing neurons to ferroptosis, a specific form of cell death. These findings reveal a critical new mechanism to protect neurons during oxidative stress that has far-reaching implications for understanding numerous neurodegenerative diseases for which ferroptosis is a main driver of neuron death.

About Isha Ralhan

Isha Ralhan is currently a PhD student in Dr. Maria Ioannou’s laboratory at the University of Alberta. As lead author of this study, Isha contributed significantly to the development of the project, data collection and analysis of the study. She wrote the first draft of the paper, made all the figures, and worked closely with her supervisor to polish the final version.

Sources of funding

Isha Ralhan is supported by a Canadian Institutes of Health Research (CIHR) Doctoral Award #181551, the Alberta Synergies in Alzheimer’s and Related Disorders program funded by the Alzheimer Society of Alberta and Northwest Territories, the University Hospital Foundation and the Neuroscience and Mental Health Institute, an Alberta Graduate Excellence Scholarship, and a 75th Anniversary Graduate Student Award from the Faculty of Medicine & Dentistry, University of Alberta.