Cited by 231Mitochondrial Function and PathologyRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

Inhibition of NADH-Linked Mitochondrial Respiration by 4-Hydroxy-2-nonenal

Humphries, Kenneth M., Yoo, Young, Szweda, Luke I.·1998·Biochemistry

Abstract

During the progression of certain degenerative conditions, including myocardial ischemia-reperfusion injury, mitochondria are a source of increased free-radical generation and exhibit declines in respiratory function(s). It has therefore been suggested that oxidative damage to mitochondrial components plays a critical role in the pathology of these processes. Polyunsaturated fatty acids of membrane lipids are prime molecular targets of free-radical damage. A major product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is highly cytotoxic and can readily react with and damage protein. In this study, the effects of HNE on intact cardiac mitochondria were investigated to gain insight into potential mechanisms by which free radicals mediate mitochondrial dysfunction. Exposure of mitochondria to micromolar concentrations of HNE caused rapid declines in NADH-linked but not succinate-linked state 3 and uncoupled respiration. The activity of complex I was unaffected by HNE under the conditions of our experiments. Loss of respiratory activity reflected the inability of HNE-treated mitochondria to meet NADH demand during maximum rates of O2 consumption. HNE exerted its effects on intact mitochondria by inactivating alpha-ketoglutarate dehydrogenase. These results therefore identify a potentially important mechanism by which free radicals bring about declines in mitochondrial respiration.

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Crossref · 10.1021/bi971958i

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Authors
Humphries, K. M., Yoo, Y., & Szweda, L. I.
Affiliations
Case Western Reserve University (US)
Venue
Biochemistry
Published
1998-01-01
Volume
37
Issue
2
Pages
552-557
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
OpenAlex
W2059545411
Cited by
231
References
22
Citations by year
2026: 5 · 2025: 4 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 10 · 2015: 4 · 2014: 3 · 2013: 7 · 2012: 11
FWCI
3.72
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
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
4-hydroxynonenal, lipid peroxidation, mitochondrial respiration, alpha-ketoglutarate dehydrogenase, free radicals, oxidative damage, myocardial ischemia-reperfusion injury, heart mitochondria, complex I, uncoupled respiration
MeSH terms
Aldehydes, Animals, Glutamate Dehydrogenase, Ketoglutarate Dehydrogenase Complex, Mitochondria, Heart, NAD, Oxygen Consumption, Sarcolemma, Uncoupling Agents, Lipid Peroxidation, NAD(P)H Dehydrogenase (Quinone), Rats, Sprague-Dawley, Cell Respiration, Rats

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