Regulation of FSP1 myristoylation by NADPH: A novel mechanism for ferroptosis inhibition

• DOI: 10.1016/j.redox.2024.103176
• Publication Date: 2024-04-30T19:08:48Z
• Authors: Na Liu; Wei-Long Wu; Xiao-Rui Wan; Jing Wang; Jia-Ni Huang; Yi-Yue Jiang; Yi-Chao Sheng; Jun-Chao Wu; Zhong-Qin Liang; Zheng-Hong Qin; Yan Wang
• Keywords: Excitotoxicity

Excitotoxicity is a prevalent pathological event in neurodegenerative diseases. The involvement of ferroptosis the pathogenesis 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 exogenous NADPH, besides being reductant, interacts N-myristoyltransferase 2 (NMT2) and upregulates N-myristoylated suppressor protein 1 (FSP1). NADPH increases membrane-localized FSP1 strengthens resistance ferroptosis. Arg-291 NMT2 critical for NADPH-NMT2-FSP1 axis-mediated suppression This study suggests plays pivotal role by bridging neuronal We propose mechanism which regulates N-myristoylation, important implications disease treatment.