New insights on iron overload-mediated lysosomal membrane rupture in liver regeneration following acetaminophen-induced liver injury.
- 1Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
- 2Department of Internal Medicine, Division of Gastroenterology, Hepatology & Mobility, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Abstract
Acetaminophen (APAP) overdose is a leading cause of liver failure in Western countries and a major clinical challenge because effective treatment options remain limited for patients who present after the optimal early therapeutic window. Iron is distributed among several subcellular compartments, such as cytosol, mitochondria, ferritin, and endosomes/lysosomes. Emerging evidence indicates that intracellular iron homeostasis and organelle function may be critical during the regeneration phase for repairing liver damage. Our recent work identified the metalloreductase six-transmembrane epithelial antigen of the prostate 4 (STEAP4) as a critical regulator of lysosomal iron homeostasis and membrane integrity during the regeneration phase following APAP overdose. Hepatic STEAP4 deficiency promoted lysosomal iron accumulation and impaired hepatocyte proliferation, whereas deferiprone-mediated iron chelation restored lysosomal function and promoted liver regeneration. In this perspective, we discuss the potential of targeting lysosomal iron to promote liver repair after APAP overdose-induced liver injury, as well as the limitations and challenges.
Related
- Leucocytes, cytokines and satellite cells: what role do they play in muscle damage and regeneration following eccentric exercise?
- Differential Protection against Acetaminophen-induced Liver and Kidney Injury by N-Acetylcysteine and Fomepizole in Female Mice
- Association between early postoperative acetaminophen exposure and acute kidney injury across surgical cohorts: a retrospective analysis of the MIMIC-IV database
- Early isolated C7 vertebral body metastasis following temporal gliosarcoma resection: Pathophysiological insights and practice-oriented management framework.
- Service use following violence: insights from the linked administrative data in South Wales
BibTeX
@article{zhu2026insights,
title = {{New insights on iron overload-mediated lysosomal membrane rupture in liver regeneration following acetaminophen-induced liver injury.}},
author = {Hualong Zhu and Peng Cao and Wen-Xing Ding},
journal = {Exploration of digestive diseases},
year = {2026},
month = sep,
doi = {10.37349/edd.2026.1005138},
url = {https://europepmc.org/article/MED/42846681},
note = {CC BY},
}
RIS
TY - JOUR
TI - New insights on iron overload-mediated lysosomal membrane rupture in liver regeneration following acetaminophen-induced liver injury.
AU - Hualong Zhu
AU - Peng Cao
AU - Wen-Xing Ding
PY - 2026
DA - 2026/09/28
JO - Exploration of digestive diseases
DO - 10.37349/edd.2026.1005138
UR - https://europepmc.org/article/MED/42846681
AB - Acetaminophen (APAP) overdose is a leading cause of liver failure in Western countries and a major clinical challenge because effective treatment options remain limited for patients who present after the optimal early therapeutic window. Iron is distributed among several subcellular compartments, such as cytosol, mitochondria, ferritin, and endosomes/lysosomes. Emerging evidence indicates that intracellular iron homeostasis and organelle function may be critical during the regeneration phase for repairing liver damage. Our recent work identified the metalloreductase six-transmembrane epithelial antigen of the prostate 4 (STEAP4) as a critical regulator of lysosomal iron homeostasis and membrane integrity during the regeneration phase following APAP overdose. Hepatic STEAP4 deficiency promoted lysosomal iron accumulation and impaired hepatocyte proliferation, whereas deferiprone-mediated iron chelation restored lysosomal function and promoted liver regeneration. In this perspective, we discuss the potential of targeting lysosomal iron to promote liver repair after APAP overdose-induced liver injury, as well as the limitations and challenges.
SN - 2833-6321
ER -