Cited by 536Redox biology and oxidative stressMitochondrial Function and PathologyCardiac Ischemia and Reperfusion

Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase

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Jo, Seung-Hee, Son, Mi-Kyung, Koh, Ho-Jin, Lee, Su-Min, Song, In-Hwan, Kim, Yong-Ou, Lee, Young-Sup, Jeong, Kyu-Shik +4 more·2001·Journal of Biological Chemistry

Abstract

Mitochondria are the major organelles that produce reactive oxygen species (ROS) and the main target of ROS-induced damage as observed in various pathological states including aging. Production of NADPH required for the regeneration of glutathione in the mitochondria is critical for scavenging mitochondrial ROS through glutathione reductase and peroxidase systems. We investigated the role of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) in controlling the mitochondrial redox balance and subsequent cellular defense against oxidative damage. We demonstrate in this report that IDPm is induced by ROS and that decreased expression of IDPm markedly elevates the ROS generation, DNA fragmentation, lipid peroxidation, and concurrent mitochondrial damage with a significant reduction in ATP level. Conversely, overproduction of IDPm protein efficiently protected the cells from ROS-induced damage. The protective role of IDPm against oxidative damage may be attributed to increased levels of a reducing equivalent, NADPH, needed for regeneration of glutathione in the mitochondria. Our results strongly indicate that IDPm is a major NADPH producer in the mitochondria and thus plays a key role in cellular defense against oxidative stress-induced damage.

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Authors
Jo, S.-H., Son, M.-K., Koh, H.-J., Lee, S.-M., Song, I.-H., Kim, Y.-O., Lee, Y.-S., Jeong, K.-S., Kim, W. B., Park, J.-W., Song, B. J., & Huhe, T.-L.
Affiliations
  • Kyungpook National University (KR)
  • Yeungnam University (KR)
  • National Institutes of Health (US)
  • Dong-A Pharmaceutical (South Korea) (KR)
Corresponding author
Huhe, Tae-Lin
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-05
Volume
276
Issue
19
Pages
16168-16176
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2131960328
Cited by
536
References
69
Citations by year
2026: 10 · 2025: 15 · 2024: 15 · 2023: 18 · 2022: 8 · 2021: 34 · 2020: 34 · 2019: 33 · 2018: 32 · 2017: 29 · 2016: 21 · 2015: 19 · 2014: 25 · 2013: 24 · 2012: 23
FWCI
6.13
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Korea Science and Engineering Foundation
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
NADP-isocitrate dehydrogenase, mitochondrial redox balance, reactive oxygen species, oxidative stress, NADPH production, glutathione regeneration, glutathione reductase, lipid peroxidation, DNA fragmentation, mitochondrial damage, ATP depletion, aging
MeSH terms
Amino Acid Sequence, Animals, Antibodies, Cattle, Cell Survival, Cloning, Molecular, Glutathione Peroxidase, Glutathione Reductase, Homeostasis, Humans, Isocitrate Dehydrogenase, Kinetics, Mitochondria, Molecular Sequence Data, Oxidation-Reduction, Peptide Fragments, Recombinant Proteins, Superoxide Dismutase, Swine, Sequence Alignment, 3T3 Cells, Apoptosis, Reactive Oxygen Species, Sequence Homology, Amino Acid, Oxidative Stress, Mice, DNA Fragmentation

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