SREBP activation contributes to fatty acid accumulations in necroptosis

About this article:

Necroptosis is a type of programmed cell death that is accompanied by extensive inflammatory activity. Previously, it has been shown that lipids accumulate in this process, and the accumulation exacerbates the membrane permeability and cell death in necroptosis.

However, the mechanisms that result in the accumulation of these lipids are unknown.

In this work, the authors used a global transcriptomics approach. They investigated the changes in the expression of proteins involved in lipid biosynthesis and transport to identify upstream mechanisms that cause lipid accumulation in necroptosis. Such a transcriptomics approach combined with further targeted experiments revealed the activation of a key regulatory mechanism of lipid production, namely sterol regulatory element binding proteins.

The authors showed that modulating the activation of sterol regulatory element binding proteins impacts necroptotic phenotype, demonstrating the functional role of these proteins in the accumulation of toxic lipids in necroptosis. Moreover, these results provide insights into mechanisms that regulate lipid production in cell death.


Infographic of SREBP activation contributes to fatty acid accumulations in necroptosis

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