AI Article Synopsis
- Excitotoxicity is a key factor in neurodegenerative diseases, and its connection to ferroptosis (a form of cell death) is not well understood.
- This study finds that NADPH not only acts as a reductant but also interacts with N-myristoyltransferase 2 (NMT2), leading to increased levels of a protein (FSP1) that helps resist ferroptosis.
- The research highlights that the interaction between NADPH, NMT2, and FSP1 is crucial for understanding how neurons can withstand ferroptosis, potentially offering new avenues for treating related diseases.
Article Abstract
Excitotoxicity is a prevalent pathological event in neurodegenerative diseases. The involvement of ferroptosis in the pathogenesis of excitotoxicity remains elusive. Transcriptome analysis has revealed that cytoplasmic reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels are associated with susceptibility to ferroptosis-inducing compounds. Here we show that exogenous NADPH, besides being reductant, interacts with N-myristoyltransferase 2 (NMT2) and upregulates the N-myristoylated ferroptosis suppressor protein 1 (FSP1). NADPH increases membrane-localized FSP1 and strengthens resistance to ferroptosis. Arg-291 of NMT2 is critical for the NADPH-NMT2-FSP1 axis-mediated suppression of ferroptosis. This study suggests that NMT2 plays a pivotal role by bridging NADPH levels and neuronal susceptibility to ferroptosis. We propose a mechanism by which the NADPH regulates N-myristoylation, which has important implications for ferroptosis and disease treatment.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074979 | PMC |
| http://dx.doi.org/10.1016/j.redox.2024.103176 | DOI Listing |
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