Related Experiment Video

Updated: Jun 3, 2026

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
08:57

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases

Published on: February 24, 2018

Mitochondrial Cu,Zn-superoxide dismutase mediates pulmonary fibrosis by augmenting H2O2 generation

Chao He1, Shubha Murthy, Michael L McCormick

  • 1Department of Internal Medicine, Carver College of Medicine,University of Iowa, Iowa City, Iowa 52242, USA.

The Journal of Biological Chemistry
|March 12, 2011
PubMed

Insights

Hydrogen peroxide (H2O2) from alveolar macrophages contributes to pulmonary fibrosis. The antioxidant enzyme copper, zinc-superoxide dismutase (Cu,Zn-SOD) moves to mitochondria, increasing H2O2 and driving fibrosis.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Pulmonary Medicine

Background:

  • Hydrogen peroxide (H2O2) release from alveolar macrophages is implicated in pulmonary fibrosis.
  • The precise source and mechanism of H2O2 production in this context remain largely unknown.

Purpose of the Study:

  • To investigate the role of copper, zinc-superoxide dismutase (Cu,Zn-SOD) in H2O2 generation and its contribution to pulmonary fibrosis pathogenesis.

Main Methods:

  • Analysis of H2O2 production and Cu,Zn-SOD expression in alveolar macrophages from asbestosis patients.
  • Investigating the translocation of Cu,Zn-SOD to the mitochondrial intermembrane space (IMS) using asbestos exposure models.
  • Utilizing Cu,Zn-SOD knockout mice and gene knockdown techniques to assess the functional relevance of Cu,Zn-SOD in H2O2 generation and fibrosis development.

Main Results:

  • Alveolar macrophages from asbestosis patients exhibit high spontaneous H2O2 production and elevated Cu,Zn-SOD expression.
  • Asbestos exposure induces Cu,Zn-SOD translocation to the mitochondrial IMS in macrophages, dependent on mitochondrial respiration and specific cysteine residues.
  • Cu,Zn-SOD-mediated H2O2 generation is linked to the iron-sulfur protein Rieske in complex III.
  • Cu,Zn-SOD knockout mice show reduced H2O2 levels, decreased oxidative stress, and protection against pulmonary fibrosis.
  • Knockdown of Cu,Zn-SOD in monocytes attenuated collagen deposition by lung fibroblasts.

Conclusions:

  • Copper, zinc-superoxide dismutase (Cu,Zn-SOD) translocates to the mitochondrial intermembrane space (IMS) in alveolar macrophages, representing a novel mechanism for increased H2O2 generation.
  • This mitochondrial Cu,Zn-SOD-driven H2O2 production plays a critical role in the pathogenesis of pulmonary fibrosis.

More Related Videos

Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase (COX/SDH) Double-labeling Histochemistry06:53

Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase (COX/SDH) Double-labeling Histochemistry

Published on: November 23, 2011

Related Concept Videos

Electron Transport Chain: Complex III and IV01:43

Electron Transport Chain: Complex III and IV

During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
The Supercomplexes in the Crista Membrane01:41

The Supercomplexes in the Crista Membrane

The mitochondrial cristae membrane is the primary site for the oxidative phosphorylation (OXPHOS) process of energy conversion mediated through respiratory complexes I to V. These complexes have been widely studied for decades, and it has been proven that they form supramolecular structures called respiratory supercomplexes (SC). These higher-order complexes may be crucial in maintaining the biochemical structure and improving the physiological activity of the individual complexes while...
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...
Chronic Obstructive Pulmonary Disease-II: Pathophysiology01:20

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...