ArticleFree radical biology & medicine2010
Reactive gamma-ketoaldehydes formed via the isoprostane pathway disrupt mitochondrial respiration and calcium homeostasis.
Article in Free radical biology & medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Mitochondrial Iron Handling and Lipid Peroxidation as Drivers of Ferroptosis.International journal of molecular sciences · 2026Review
- Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease.Biomedicines · 2025Review
- Article
- The MT1 receptor as the target of ramelteon neuroprotection in ischemic stroke.Journal of pineal research · 2024Article
- A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells.Chemical science · 2021Article
- Mitochondrial Isolevuglandins Contribute to Vascular Oxidative Stress and Mitochondria-Targeted Scavenger of Isolevuglandins Reduces Mitochondrial Dysfunction and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Highly Reactive Isolevuglandins Promote Atrial Fibrillation Caused by Hypertension.JACC. Basic to translational science · 2020Article
- Targeting of reactive isolevuglandins in mitochondrial dysfunction and inflammation.Redox biology · 2019Article
- Isolevuglandins and cardiovascular disease.Prostaglandins & other lipid mediators · 2018Review
- Scavenging of highly reactive gamma-ketoaldehydes attenuates cognitive dysfunction associated with epileptogenesis.Neurobiology of disease · 2017Article
- Accumulation of isolevuglandin-modified protein in normal and fibrotic lung.Scientific reports · 2016Article
- Decreased Bioenergetic Health Index in monocytes isolated from the pericardial fluid and blood of post-operative cardiac surgery patients.Bioscience reports · 2015Article
- Isolevuglandin adducts in disease.Antioxidants & redox signaling · 2015Review
- Qualitative characterization of the rat liver mitochondrial lipidome using all ion fragmentation on an Exactive benchtop Orbitrap MS.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Mass spectrometry detection of isolevuglandin adduction to specific protein residues.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Soluble, prefibrillar α-synuclein oligomers promote complex I-dependent, Ca2+-induced mitochondrial dysfunction.The Journal of biological chemistry · 2014Article
- Lipid peroxidation generates biologically active phospholipids including oxidatively N-modified phospholipids.Chemistry and physics of lipids · 2014Review
- N-acetyl-serotonin offers neuroprotection through inhibiting mitochondrial death pathways and autophagic activation in experimental models of ischemic injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Pretreatment with pyridoxamine mitigates isolevuglandin-associated retinal effects in mice exposed to bright light.The Journal of biological chemistry · 2013Article
- Posttranslational modification by an isolevuglandin diminishes activity of the mitochondrial cytochrome P450 27A1.Journal of lipid research · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Isoketals (IsoKs) are gamma-ketoaldehydes formed via the isoprostane pathway of arachidonic acid peroxidation and are among the most reactive by-products of lipid peroxidation. IsoKs selectively adduct to protein lysine residues and are highly cytotoxic, but the targets and molecular events involved in IsoK-induced cell death are poorly defined. Our previous work established that physiologically relevant aldehydes induce mitochondrial dysfunction (Kristal et al., J. Biol. Chem.271:6033-6038; 1996). We therefore examined whether IsoKs induced mitochondrial dysfunction. Incubation of mitochondria with synthetic IsoKs in the presence or absence of Ca(2+) was associated with alterations in mitochondrial respiration, membrane potential (DeltaPsi), and pyridine nucleotide redox state. IsoKs dose dependently (0.5-4microM) accelerated liver mitochondria swelling induced by low concentrations of Ca(2+) and Zn(2+) or by the prooxidant tert-butylhydroperoxide, and release of cytochrome c, with similar observations in heart/brain mitochondria. The mitochondrial permeability transition (mPT) inhibitor cyclosporine A delayed IsoK-induced mitochondria dysfunction. The actions of IsoKs are consistent with interactions with cytochrome c, a protein rich in lysine residues. Direct reaction of IsoKs with select lysines in cytochrome c was demonstrated using high-resolution mass spectrometry. Overall, these results suggest that IsoKs may, in part, mediate their cytotoxic effects through induction of the mPT and subsequent activation of downstream cell death cascades.
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