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Columbia researchers have found that a rare type of lipid is a key driver of pheroptosis, a form of cell death discovered by Columbia professor Brent Stockwell.

The findings provide new insights into how cells die during pheroptosis and may improve understanding of how to prevent pheroptosis in contexts where it is becoming detrimental—neurodegenerative. in diseases, for example—or include it in contexts where it is useful, such as consumption. To kill dangerous cancer cells.

The new study found that a rare type of lipid with two polyunsaturated fatty acyl tails, called dPUFA phospholipids, was present in contexts where ferroptosis was occurring, including aging. In the brain and brain tissue affected by Huntington’s disease. Findings show that the lipid is effective in promoting ferroptosis.

The research was conducted by professors from Columbia’s Department of Biological Sciences, Department of Chemistry, and Columbia University Irving Medical Center.

Stockwell first discovered pheroptosis in 2012, when he found that some cells were dying because their lipid layers were collapsing—an unusual form of cell death that differs from the most common type. , which starts from a blistering cell on its outer surface. Since that discovery, researchers in Stockwell’s lab and elsewhere have continued to investigate pheroptosis, discovering that it can occur naturally in aging cells, in pathological contexts, and in the treatment of disease. can be induced. Another paper this month with several co-authors found that a gene called PHLDA2 can sometimes promote apoptosis by attacking a different lipid, and that the gene can prevent some tumors from forming. Together, these papers show that specific lipids promote apoptosis, so elucidation of driver lipids in specific cancers is important.

“The discovery that these dPUFA lipids are key drivers of pheroptosis deepens our understanding of this form of cell death, and their role in controlling cell homeostasis in general,” said Stockwell. The Role of Lipids”. “Using these lipids may ultimately help us identify where apoptosis has occurred and deliberately manipulate them to either cause or prevent cell death. can have both the understanding and the power to control death.”

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