Oxidatively damaged proteins of heart mitochondrial electron transport complexes
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Protein modifications, such as carbonylation, nitration and formation of lipid peroxidation adducts, e.g. 4-hydroxynonenal (HNE), are products of oxidative damage attributed to reactive oxygen species (ROS). The mitochondrial respiratory chain Complexes I and III have been shown to be a major source of ROS in vitro. Additionally, modifications of the respiratory chain Complexes (I-V) by nitration, carbonylation and HNE adduct decrease their enzymatic activity in vitro. However, modification of these respiratory chain complex proteins due to in vivo basal level ROS generation has not been investigated. In this study, we show a basal level of oxidative damage to specific proteins of adult bovine heart submitochondrial particle (SMP) complexes, and find that most of these proteins are localized in the mitochondrial matrix. We postulate that electron leakage from respiratory chain complexes and subsequent ROS formation may cause damage to specific complex subunits and contribute to long-term accumulation of mitochondrial dysfunction.
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Although nonmitochondrial sources of ROS exist during ischemia, the majority of ROS are likely derived from the mitochondrial respiratory complexes.
“Although nonmitochondrial sources of ROS exist during ischemia [e.g., NAD(P)H oxidase (141, 188, 328) and xanthine oxidase (25) in vasculature], the majority of ROS are likely derived from the mitochondrial respiratory complexes, as shown by the damage to respiratory complexes (212, 213, 245) and the effect of mitochondrial inhibitors (5, 28, 71, 81–86).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [84]
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“Estas estructuras químicas para estabilizarse reaccionan rápidamente con moléculas adyacentes mediante reacciones de oxido-reducción, dañando biomoléculas, como carbohidratos, proteínas, lípidos y ADN, y, por consiguiente, afectando la membrana plasmática y organelas, como la mitocondria y el núcleo celular (5).”
Background
- Authors
- Choksi, K. B., Boylston, W. H., Rabek, J. P., Widger, W. R., & Papaconstantinou, J.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- University of Houston (US)
- Corresponding author
- Papaconstantinou, J.
- ORCID
- Widger, W.R.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2004-03
- Volume
- 1688
- Issue
- 2
- Pages
- 95-101
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W2155227094
- Cited by
- 212
- References
- 39
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 10 · 2020: 9 · 2019: 8 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 13 · 2013: 12 · 2012: 14
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israeli Centers for Research Excellence
- National Institute on Aging (P02 AG10514, P30AG024832)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- oxidative protein damage, heart mitochondria, respiratory chain complexes, protein carbonylation, nitration, reactive oxygen species, electron leakage, mitochondrial dysfunction, submitochondrial particles, mitochondrial matrix proteins
- MeSH terms
- Aldehydes, Animals, Cattle, Electrophoresis, Polyacrylamide Gel, Intracellular Membranes, Mitochondria, Heart, Oxidation-Reduction, Oxygen Consumption, Submitochondrial Particles, Tyrosine, Immunoblotting, Reactive Oxygen Species, Protein Structure, Tertiary, Porins, Adenine Nucleotide Translocator 1, Electron Transport Chain Complex Proteins, Voltage-Dependent Anion Channels
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