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Updated: May 6, 2026

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

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Targeting mitochondrial phosphatase PGAM5 alleviates ferroptosis and acute pancreatitis by upregulating NRF2-mediated

Shuang Ma1, Jianhua Qin1, Jing Luan1

  • 1The HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.

Cell Death & Disease
|February 21, 2026
PubMed

Insights

Phosphoglycerate mutase 5 (PGAM5) regulates ferroptosis, a cell death pathway. Modulating PGAM5 protects cells by upregulating protective proteins, offering potential therapeutic strategies for conditions like acute pancreatitis.

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Pathology

Background:

  • Ferroptosis is iron-dependent necrosis involving lipid peroxidation.
  • Phosphoglycerate mutase 5 (PGAM5) is a mitochondrial hub regulating dynamics and stress.
  • PGAM5's role in ferroptosis was previously unclear.

Purpose of the Study:

  • To elucidate the function of PGAM5 in ferroptosis.
  • To investigate the molecular mechanisms by which PGAM5 influences ferroptosis.
  • To explore the therapeutic potential of targeting PGAM5 in acute pancreatitis.

Main Methods:

  • Genetic deletion and overexpression of PGAM5.
  • Analysis of nuclear factor erythroid 2-related factor 2 (NRF2) and ferroptosis suppressor protein 1 (FSP1) expression.
  • Measurement of cellular energy stress and AMP-activated protein kinase (AMPK) activation.
  • Pharmacological inhibition of PGAM5 in an acute pancreatitis model.

Main Results:

  • PGAM5 dysregulation protects against ferroptosis by upregulating NRF2-mediated FSP1 expression.
  • PGAM5 modulation increases the AMP/ATP ratio, activating AMPK.
  • AMPK activation promotes NRF2 nuclear accumulation and FSP1 transcription.
  • Pharmacological PGAM5 inhibition reduced severity in arginine-induced acute pancreatitis.

Conclusions:

  • PGAM5 is a critical regulator of ferroptosis.
  • PGAM5 influences cell survival through the NRF2/FSP1 pathway via AMPK activation.
  • Targeting PGAM5 shows therapeutic promise for acute pancreatitis.

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