Related Experiment Video

Updated: Jun 26, 2026

Experimental Protocol for Detecting Mitochondrial Function in Hepatocytes Exposed to Organochlorine Pesticides
08:39

Experimental Protocol for Detecting Mitochondrial Function in Hepatocytes Exposed to Organochlorine Pesticides

Published on: September 16, 2020

Acetaldehyde impairs mitochondrial glutathione transport in HepG2 cells through endoplasmic reticulum stress

Josep M Lluis1, Anna Colell, Carmen García-Ruiz

  • 1Liver Unit, Institut of Malalties Digestives, Hospital Clinic i Provincial, IDIBAPS, Department of Experimental Pathology, IIBB, Consejo Superior Investigaciones Científicas, Barcelona, Spain.

Gastroenterology
|March 4, 2003
PubMed
Abstract

Insights

Acetaldehyde impairs mitochondrial glutathione (GSH) transport in HepG2 cells by increasing mitochondrial cholesterol, sensitizing them to TNF-alpha-induced apoptosis. This occurs via endoplasmic reticulum stress, affecting cellular defense mechanisms.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Hepatology

Background:

  • Ethanol consumption negatively impacts cellular energy production by disrupting mitochondrial function.
  • Reduced glutathione (GSH) is crucial for mitochondrial health, and its transport is sensitive to ethanol metabolites.
  • Acetaldehyde, a primary ethanol metabolite, is investigated for its specific effects on mitochondrial GSH (mGSH) regulation.

Purpose of the Study:

  • To elucidate the role of acetaldehyde in regulating mGSH levels within HepG2 cells.
  • To investigate the mechanisms by which acetaldehyde affects mGSH transport and mitochondrial integrity.

Main Methods:

  • HepG2 cells were treated with acetaldehyde, and subsequent analyses included mGSH levels, GSH transport kinetics, mitochondrial membrane microviscosity, and lipid composition.
  • Mitochondria isolated from treated cells were used to assess GSH transport parameters (Michaelis constant).
  • Gene expression related to endoplasmic reticulum (ER) stress and cholesterol metabolism was analyzed.

Main Results:

  • Acetaldehyde treatment led to a dose- and time-dependent depletion of mGSH, while cytosolic GSH remained unaffected.
  • GSH transport into mitochondria exhibited two saturable components, both negatively impacted by acetaldehyde, indicating impaired transport.
  • Increased mitochondrial cholesterol deposition, linked to ER stress markers (GADD153, SREBP-1), was identified as the cause of impaired GSH transport.

Conclusions:

  • Acetaldehyde disrupts mitochondrial function by impairing GSH transport, mediated by ER stress-induced cholesterol accumulation.
  • This impairment of mGSH homeostasis sensitizes HepG2 cells to TNF-alpha-induced apoptosis.
  • Therapeutic interventions targeting cholesterol or enhancing GSH levels may mitigate acetaldehyde's toxic effects.

More Related Videos

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays08:03

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays

Published on: March 7, 2025

Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer08:37

Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer

Published on: November 15, 2024

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...
The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation01:22

Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation

Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Hepatic Encephalopathy01:29

Hepatic Encephalopathy

DefinitionHepatic encephalopathy is a reversible neurologic syndrome that results from advanced liver dysfunction or portosystemic shunting. It leads to disturbances in cognition, behavior, and motor function due to the brain’s exposure to gut-derived toxins that the liver fails to detoxify.EtiologyThis condition develops either in the setting of acute fulminant hepatitis or progressively during chronic liver disease, such as cirrhosis and portal hypertension. Portosystemic shunting—including...