Related Experiment Video

Updated: Jul 16, 2025

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro
13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

10.4K

Mitochondrial IRG1 traps MCL-1 to induce hepatocyte apoptosis and promote carcinogenesis

Liyuan Zhang1, Yue Dong1, Luxin Zhang1

  • 1National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.

Cell Death & Disease
|September 22, 2023
PubMed

Insights

Immunoresponsive gene 1 (IRG1) promotes liver cancer by inducing hepatocyte apoptosis. This finding reveals IRG1 as a potential therapeutic target for preventing liver injury and hepatocellular carcinoma (HCC).

Area of Science:

  • Hepatology
  • Molecular Biology
  • Cancer Research

Background:

  • Hepatocarcinogenesis involves hepatocyte death and liver damage, with underlying mechanisms requiring further investigation.
  • Immunoresponsive gene 1 (IRG1) and itaconate are known to regulate inflammation in myeloid cells, but their role in liver parenchymal cells and hepatocarcinogenesis is unclear.

Purpose of the Study:

  • To investigate the role of IRG1 in diethylnitrosamine (DEN)-induced hepatocarcinogenesis.
  • To elucidate the mechanisms by which IRG1 influences hepatocyte apoptosis and liver injury.

Main Methods:

  • Utilized a diethylnitrosamine (DEN)-induced mouse model of hepatocarcinogenesis.
  • Assessed IRG1 expression in hepatocytes following DEN administration.
  • Investigated the molecular mechanisms of IRG1-mediated apoptosis, including mitochondrial localization and protein interactions.

Main Results:

  • Hepatocyte IRG1 expression was significantly induced by DEN administration.
  • DEN-induced IRG1 promoted intrinsic mitochondrial apoptosis of hepatocytes and exacerbated liver damage, thereby enhancing hepatocarcinogenesis.
  • Mitochondrial IRG1 was found to bind MCL-1, inhibiting its interaction with Bim, leading to Bim activation, Bax translocation, and apoptosis initiation.

Conclusions:

  • Inducible mitochondrial IRG1 promotes hepatocyte apoptosis and subsequent hepatocarcinogenesis.
  • IRG1 plays a critical role in liver injury and the development of hepatocellular carcinoma (HCC).
  • IRG1 represents a potential therapeutic target for preventing liver injury and HCC.

More Related Videos

Author Spotlight: Detection of Mitophagy in Caenorhabditis elegans and Mammalian Cells Using Organelle-Specific Dyes11:59

Author Spotlight: Detection of Mitophagy in Caenorhabditis elegans and Mammalian Cells Using Organelle-Specific Dyes

Published on: May 19, 2023

2.3K
Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms11:36

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms

Published on: May 29, 2020

3.0K

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
14.3K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.6K
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.3K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.1K