Malic Enzyme 1 as a Novel Anti-Ferroptotic Regulator in Hepatic Ischemia/Reperfusion Injury.

ABSTRACT: Ferroptosis has been linked to the pathogenesis of hepatic injury induced by ischemia/reperfusion (I/R). However, the mechanistic basis remains unclear. In this study, by using a mouse model of hepatic I/R injury, it is observed that glutathione (GSH) and cysteine depletion are associated with deficiency of the reducing power of nicotinamide adenine dinucleotide phosphate (NADPH). Genes involved in maintaining NADPH homeostasis are screened, and it is identified that I/R-induced hepatic ferroptosis is significantly associated with reduced expression and activity of NADP⁺ -dependent malic enzyme 1 (Me1). Mice with hepatocyte-specific Me1 gene deletion exhibit aggravated ferroptosis and liver injury under I/R treatment; while supplementation with L-malate, the substrate of ME1, re

SUBMITTER: Fang X 

PROVIDER: S-EPMC10161122 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature