Related Experiment Video

Updated: Jun 13, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

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

Published on: March 15, 2024

898

MMP9 drives ferroptosis by regulating GPX4 and iron signaling

Flobater I Gawargi1, Paras K Mishra1

  • 1Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.

Iscience
|September 10, 2024
PubMed

Insights

Matrix metalloproteinase-9 (MMP9) critically regulates ferroptosis, a cell death form driven by iron overload and glutathione peroxidase-4 (GPX4) suppression. MMP9 impacts GPX4 levels, iron balance, and cellular redox state, offering a potential therapeutic target.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Medicine

Background:

  • Ferroptosis is a regulated cell death pathway characterized by glutathione peroxidase-4 (GPX4) inhibition and iron accumulation.
  • Understanding the molecular mechanisms controlling ferroptosis is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of matrix metalloproteinase-9 (MMP9) in regulating ferroptosis.
  • To elucidate the molecular interactions and pathways through which MMP9 influences ferroptosis.

Main Methods:

  • Utilized an innovative MMP9 construct lacking collagenase activity.
  • Employed Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) to identify protein interactors.
  • Performed Integrated Pathway Analysis (IPA) to analyze affected cellular pathways.

Main Results:

  • Active MMP9 directly interacts with GPX4 and glutathione reductase, decreasing GPX4 expression and activity.
  • MMP9 suppresses key transcription factors (SP1, CREB1, NRF2, FOXO3, ATF4), GPX1, and ferroptosis suppressor protein-1 (FSP1), disrupting cellular redox balance.
  • MMP9 modulates iron metabolism and interacts with 83 subcellular proteins involved in ferroptosis regulation.

Conclusions:

  • MMP9 is a significant regulator of ferroptosis, impacting GPX4, iron homeostasis, and cellular redox balance.
  • MMP9's extensive influence on ferroptosis pathways suggests its potential as a therapeutic target for diseases involving redox and iron dysregulation.
Keywords:
cell biologymolecular biology

More Related Videos

Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts09:21

Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts

Published on: February 23, 2024

856
Setup of Capillary Electrophoresis-Inductively Coupled Plasma Mass Spectrometry CE-ICP-MS for Quantification of Iron Redox Species FeII, FeIII04:48

Setup of Capillary Electrophoresis-Inductively Coupled Plasma Mass Spectrometry CE-ICP-MS for Quantification of Iron Redox Species FeII, FeIII

Published on: May 4, 2020

8.0K

Related Concept Videos

Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.4K
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.3K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K