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Parisi et al manuscript and SI 2019.pdf (2.09 MB)

Membrane Disruption by Very Long Chain Fatty Acids During Necroptosis

submitted on 02.05.2019, 22:59 and posted on 06.05.2019, 16:52 by Laura Parisi, Shahin Sowlati-Hashjin, Ilyas Berhane, Kevin Carter, Jonathan Lovell, Sherry Chemler, Mikko Karttunen, G. Ekin Atilla-Gokcumen
In this work we investigate the mechanisms by which very long chain fatty acids (VLCFA) contribute to membrane permeabilization during necroptosis, a form of highly regulated necrotic cell death. We show that inactivating fatty acid elongase ELOVL7 prevents VLCFA accumulation and necroptotic cell death, while it's overexpression causes membrane permeabilization. We show that VLCFA can directly permeabilize lipid bilayers and investigate the basis of these effects by molecular dynamics simulations. Finally, we show that VLCFA can be used as substrates for protein fatty acylation during necroptosis, suggesting another potential mechanism by which VLCFA may mediate membrane permeabilization.


NSF MCB1817468

NSF 1555220

NIH R01EB017270

NIH DP5OD017898

NIH GM078383


Email Address of Submitting Author


University at Buffalo, The State University of New York


United States of America

ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no competing financial interests.