Hepatic HDAC3 Regulates Systemic Iron Homeostasis and Ferroptosis via the Hippo Signaling Pathway.

ABSTRACT: Histone deacetylases (HDACs) are epigenetic regulators that play an important role in determining cell fate and maintaining cellular homeostasis. However, whether and how HDACs regulate iron metabolism and ferroptosis (an iron-dependent form of cell death) remain unclear. Here, the putative role of hepatic HDACs in regulating iron metabolism and ferroptosis was investigated using genetic mouse models. Mice lacking Hdac3 expression in the liver (Hdac3-LKO mice) have significantly reduced hepatic Hamp mRNA (encoding the peptide hormone hepcidin) and altered iron homeostasis. Transcription profiling of Hdac3-LKO mice suggests that the Hippo signaling pathway may be downstream of Hdac3. Moreover, using a Hippo pathway inhibitor and overexpressing the transcriptional

SUBMITTER: Meng H 

PROVIDER: S-EPMC10687581 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature