N⁶-methyladenosine modification regulates ferroptosis through autophagy signaling pathway in hepatic stellate cells.

ABSTRACT: Ferroptosis is a recently identified non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation. However, the underlying exact mechanisms remain poorly understood. Here, we report that the total levels of N⁶-methyladenosine (m⁶A) modification are evidently increased upon exposure to ferroptosis-inducing compounds due to the upregulation of methylase METTL4 and the downregulation of demethylase FTO. Interestingly, RNA-seq shows that m⁶A modification appears to trigger autophagy activation by stabilizing BECN1 mRNA, which may be the potential mechanism for m⁶A modification-enhanced HSC ferroptosis. Importantly, YTHDF1 is identified as a key m⁶A reader protein for BECN1 mRNA stability, and knockdown of YTHDF1 coul

SUBMITTER: Shen M 

PROVIDER: S-EPMC8495178 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature