Transferrin promotes fatty acid oxidation and liver tumor growth through PHD2-mediated PPARα hydroxylation in an iron-dependent manner.

ABSTRACT: Tumor cells reshape iron and lipid metabolism for their rapid proliferation. However, how tumor cells coordinate the interplay between tumor cell-specific iron homeostasis and lipid metabolism reprogramming to counteract energy shortages remains unclear. Here, we demonstrated that glucose deprivation in hepatocellular carcinoma (HCC) cells induced AMPK-dependent Transferrin S685 phosphorylation, which exposed Transferrin nuclear localization signal (NLS) for binding to importin α7 and subsequent nuclear translocation. Nucleus-translocated Transferrin interacts with PPARα and enhance its protein stability to increase fatty acid oxidation (FAO) upon glucose deprivation. Mechanistically, PPARα-associated Transferrin upregulates iron-dependent PHD2-mediated PPARα P87 hydroxylation and subseque

SUBMITTER: Qian X 

PROVIDER: S-EPMC11804496 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature