JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Phosphoglycerate mutase 5 exacerbates liver ischemia-reperfusion injury by activating mitochondrial fission

  • 0Henan Engineering Technology Research Center of Organ Transplantation, Zhengzhou, 450052, Henan, China.
Scientific Reports +

|

April 12, 2024

|

April 12, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Phosphoglycerate mutase 5 (PGAM5) drives liver injury by promoting mitochondrial fission. Silencing PGAM5 protects hepatocytes from ischemia-reperfusion injury, revealing a novel therapeutic target.

Area Of Science

  • Hepatology
  • Mitochondrial Biology
  • Cell Death Pathways

Background

  • Liver ischemia-reperfusion (I/R) injury involves hepatocyte death, but its regulation remains unclear.
  • Phosphoglycerate mutase 5 (PGAM5), a mitochondrial phosphatase, influences apoptosis and necrosis.
  • The specific role of PGAM5 in I/R-induced hepatocyte death requires elucidation.

Purpose Of The Study

  • To investigate the role of PGAM5 in liver I/R injury.
  • To explore the molecular mechanisms underlying PGAM5's function in this context.

Main Methods

  • Utilized a PGAM5-silenced mice model.
  • Assessed hepatocyte death, mitochondrial function (membrane potential, DNA copy number, transcription, ROS generation, mPTP opening), and mitochondrial fission markers (Drp1 phosphorylation).
  • Administered Mdivi-1, a mitochondrial fission inhibitor.

Main Results

  • PGAM5 expression was elevated in liver I/R injury.
  • PGAM5 silencing reduced I/R-induced hepatocyte death.
  • PGAM5 silencing preserved mitochondrial function and inhibited ROS generation.
  • PGAM5 silencing decreased Drp1 phosphorylation and mitochondrial fission.
  • Mdivi-1 treatment mimicked these protective effects.

Conclusions

  • PGAM5 promotes hepatocyte death during liver I/R injury.
  • PGAM5 exacerbates liver I/R injury by inducing mitochondrial fission.
  • Targeting PGAM5 or mitochondrial fission presents a potential therapeutic strategy for liver I/R injury.

Keywords:

Related Concept Videos

Muscle Recovery and Fatigue 01:24

2.1K

Muscle fatigue refers to the decline in a muscle's ability to maintain the force of contraction after prolonged activity. It primarily stems from changes within muscle fibers. Even before experiencing muscle fatigue, one may feel tired and have the urge to stop the activity. This response, known as central fatigue, occurs due to changes in the central nervous system, namely the brain and spinal cord. While there is no single mechanism that induces fatigue, it may serve as a protective...

ATP Synthase: Mechanism 01:48

14.6K

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...

The Electron Transport Chain 01:30

16.7K

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...