GSSG-mediated Complex I defect in isolated cardiac mitochondria
The mitochondrial respiratory chain represents the major source of reactive oxygen species (ROS) in cells and its dysfunction may contribute to the pathogenesis of several diseases. In mitochondria, glutathione is the major redox buffer and is a good indicator for the redox environment of the cell. Indeed, overproduction of ROS decreases the ratio between reduced and oxidized glutathione leading the latter to bind to proteins by a mechanism called glutathionylation. In this study, we demonstrate that in isolated cardiac mitochondria the respiratory chain enzyme Complex I is highly susceptible to glutathionylation under conditions of oxidative stress, showing a significant dose- and time-dependent decrease of the activity after treatment with oxidized glutathione. Among respiratory chain enzymes, Complex I appears the most affected by the oxidant-mediated inactivation in isolated mitochondria. Also, in cultured cardiomyocytes CI activity was strongly inhibited after in vivo treatment with hydrogen peroxide. Noteworthy, HPLC analysis showed a significant increase of protein glutathionylation in oxidatively stressed cells and this rise is in vivo reverted after incubation of cells with anti-oxidant N-acetyl-cysteine. These findings take particular importance given that CI represents the entry point of electrons into oxidative phos-phorylation and that the threshold at which CI dysfunction affects ATP production is lower than that of any other OXPHOS complexes, making the enzyme particularly critical for the health of cells.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
Document Type: Research Article
Affiliations: Molecular Medicine Unit, Children's Hospital and Research Institute ‘Bambino Gesù’, Rome, Italy
Publication date: July 1, 2010
More about this publication?
- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
- Editorial Board
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Information for Advertisers
- Terms & Conditions
- Ingenta Connect is not responsible for the content or availability of external websites