Related Experiment Video

Updated: Aug 29, 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

Cu/Zn superoxide dismutase can form pore-like structures

Jinhyuk Chung1, Hoichang Yang, Mitchel D de Beus

  • 1Rensselaer Polytechnic Institute, Department of Chemistry, 110 8th street, Troy, NY 12180, USA.

Biochemical and Biophysical Research Communications
|December 4, 2003
PubMed

Insights

Mutations in copper/zinc superoxide dismutase (SOD) linked to familial amyotrophic lateral sclerosis cause toxic pore formation in vitro. This aggregation of oxidatively damaged SOD may play a role in motor neuron death in FALS.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Genetics

Background:

  • Familial amyotrophic lateral sclerosis (FALS) is a neurodegenerative disease characterized by motor neuron death.
  • Mutations in copper/zinc superoxide dismutase (SOD) are genetically linked to FALS.
  • The exact mechanism of mutant SOD toxicity in FALS remains unclear.

Purpose of the Study:

  • To investigate the mechanism by which mutant SOD proteins become toxic.
  • To explore the in vitro aggregation properties of wild-type and mutant SOD proteins.

Main Methods:

  • Utilized wild-type SOD and three pathogenic mutants (A4V, G37R, G85R).
  • Induced copper-dependent oxidation of metal-depleted SOD.
  • Analyzed protein aggregation using atomic force microscopy.

Main Results:

  • Copper-induced oxidation of metal-depleted SOD led to in vitro aggregation.
  • Aggregated SOD formed distinct pore-like structures.
  • Observed aggregation in both wild-type and mutant SOD, with potential differences in mutant behavior.

Conclusions:

  • Aberrant self-assembly of oxidatively damaged SOD mutants into toxic oligomers or pores is a potential pathological mechanism in FALS.
  • These findings suggest a novel pathway for neurodegeneration in FALS.
  • The formation of toxic pores aligns with pathogenic mechanisms observed in other neurodegenerative diseases.

More Related Videos

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess07:35

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

Confocal Imaging of Single Mitochondrial Superoxide Flashes in Intact Heart or In Vivo12:06

Confocal Imaging of Single Mitochondrial Superoxide Flashes in Intact Heart or In Vivo

Published on: November 5, 2013

Related Concept Videos

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 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...
Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...
Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
Peroxisomes01:30

Peroxisomes

Peroxisomes and mitochondria are two important oxygen-utilizing organelles in eukaryotic cells. Mitochondria carry out cellular respiration—the process that converts energy from food into ATP. Peroxisomes carry out a variety of functions, primarily breaking down different substances, such as fatty acids.The peroxisome is a single membrane-bound cellular organelle that can perform several different functions, including lipid metabolism and chemical detoxification. The enzymes within peroxisomes...
Protein Modifications in the RER01:26

Protein Modifications in the RER

Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.