Related Experiment Video

Updated: Nov 12, 2025

Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer
08:37

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

Published on: November 15, 2024

526

AMPK protects against alcohol-induced liver injury through UQCRC2 to up-regulate mitophagy

Xinyi Lu1, Wenting Xuan2, Juanjuan Li1

  • 1Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.

Autophagy
|March 15, 2021
PubMed

Insights

AMP-activated protein kinase (AMPK) protects against alcoholic liver disease by enhancing mitophagy. AMPK activates the NFE2L2-UQCRC2 pathway, improving mitochondrial function and reducing liver injury.

Area of Science:

  • * Molecular Biology
  • * Cellular Biology
  • * Hepatology

Background:

  • * Mitophagy is crucial for removing damaged mitochondria and reducing reactive oxygen species (ROS), offering protection against alcohol-induced liver injury.
  • * AMP-activated protein kinase (AMPK) is implicated in alcoholic liver disease (ALD) and mitochondrial dysfunction, but its role in regulating mitophagy in ALD is unclear.

Purpose of the Study:

  • * To investigate the mechanism by which AMPK regulates mitophagy in alcoholic liver disease.
  • * To identify key molecular players in the AMPK-mediated mitophagy pathway relevant to ALD.

Main Methods:

  • * Investigated the effect of AMPK activation on alcohol-induced liver injury and hepatocyte mitophagy.
  • * Utilized knockdown (KD) and overexpression (OE) of UQCRC2 to assess its role in mitophagy.
  • * Employed RNA-seq, chromatin immunoprecipitation (ChIP) assays, bioinformatics, and luciferase assays to elucidate gene transcription regulation.

Main Results:

  • * AMPK activation significantly reduced alcohol-induced liver injury and enhanced hepatocyte mitophagy.
  • * AMPK rescued alcohol-induced downregulation of UQCRC2, a protein critical for mitophagy.
  • * UQCRC2 knockdown impaired mitophagy, while overexpression attenuated liver injury.
  • * AMPK was found to indirectly upregulate UQCRC2 protein levels by enhancing its gene transcription via the AMPK-NFE2L2/NRF2 signaling axis.

Conclusions:

  • * AMPK plays a protective role in alcoholic liver disease by promoting mitophagy.
  • * The novel signaling axis AMPK-NFE2L2-UQCRC2 is identified as a key regulator of mitophagy in the liver.
  • * Targeting this pathway presents a potential therapeutic strategy for treating alcoholic liver disease.
Keywords:
AMPKbioinformaticsmitophagyrna-seqtranscription factoruqcrc2

More Related Videos

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy07:40

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy

Published on: May 26, 2023

1.4K
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

19.4K

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...
16.7K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.8K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.5K
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...
2.8K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.2K