Related Experiment Video
Updated: Mar 28, 2026

Atomic Absorbance Spectroscopy to Measure Intracellular Zinc Pools in Mammalian Cells
Published on: May 16, 2019
Metallothionein Safeguards Hepatic Zn-Fe Homeostasis and Restrains Yap-Driven Hepatic Fe Overload to Protect Against
Yinrui Feng1,2, Zhenfang Zhou2, Ying Xiao2
1Laboratory of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
Background:
Redox-active iron (Fe) overload and antioxidant zinc (Zn) deficiency are hallmarks of chronic liver fibrosis, yet their upstream regulatory mechanisms remain elusive.
Objective:
Here, we identify the redox-sensitive metallothionein (MT) as a critical regulator in the injured liver that integrates trace-metal homeostasis with Hippo-Yap signalling.
Methods & Results:
MT expression was transiently induced in early-stage murine and human liver fibrosis but declined sharply in advanced disease. Genetic deletion of MT in mice exacerbated CCl4-induced liver injury, characterized by severe Zn depletion, pathological Fe accumulation, and aggravated fibrosis. Mechanistically, MT loss impaired the activity of Zn-dependent matrix metalloproteinases and unleashed pathological Fe deposition, which amplified lipid peroxidation and oxidative damage. We revealed that MT deficiency suppressed the upstream Hippo kinase Mst1, promoting the nuclear translocation and activation of the transcriptional coactivator Yap. Crucially, pharmacological inhibition of Yap with verteporfin rescued the Fe overload and attenuated fibrosis in MT-deficient livers but did not correct the Zn depletion, establishing Yap as a key downstream driver of Fe dysregulation. The analysis of human fibrotic and cirrhotic livers confirmed a conserved inverse correlation between MT levels and nuclear Yap accumulation, accompanied by severe Fe deposition.
Conclusions:
These findings reveal MT as a key hepatocyte integrator of trace-metal homeostasis and Yap signalling and suggest that therapeutic strategies enhancing MT activity or combining Zn supplementation with Yap inhibition may offer new avenues to prevent or reverse chronic liver fibrosis.
More Related Videos
11:04Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides
Published on: September 7, 2019
07:32Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining
Published on: May 23, 2025
Related Concept Videos
Microbes and Other Elemental Cycles
Liver Physiology
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
The Early Endosome: Endocytosis of Transferrin
The Periodic Table and Organismal Elements
The Periodic Table and Organismal Elements
Periodic Table Provides Information...
Sulfur Assimilation