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Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase.
J Biol Chem. 2001 May 11; 276(19):16168-76.JB

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.

Authors+Show Affiliations

Departments of Genetic Engineering and Biochemistry, Kyungpook National University, Taegu 702-701, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11278619

Citation

Jo, S H., et al. "Control of Mitochondrial Redox Balance and Cellular Defense Against Oxidative Damage By Mitochondrial NADP+-dependent Isocitrate Dehydrogenase." The Journal of Biological Chemistry, vol. 276, no. 19, 2001, pp. 16168-76.
Jo SH, Son MK, Koh HJ, et al. Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase. J Biol Chem. 2001;276(19):16168-76.
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., Huh, T. L., & Huhe, T. L. (2001). Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase. The Journal of Biological Chemistry, 276(19), 16168-76.
Jo SH, et al. Control of Mitochondrial Redox Balance and Cellular Defense Against Oxidative Damage By Mitochondrial NADP+-dependent Isocitrate Dehydrogenase. J Biol Chem. 2001 May 11;276(19):16168-76. PubMed PMID: 11278619.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase. AU - Jo,S H, AU - Son,M K, AU - Koh,H J, AU - Lee,S M, AU - Song,I H, AU - Kim,Y O, AU - Lee,Y S, AU - Jeong,K S, AU - Kim,W B, AU - Park,J W, AU - Song,B J, AU - Huh,T L, AU - Huhe,T L, Y1 - 2001/02/13/ PY - 2001/3/30/pubmed PY - 2001/6/15/medline PY - 2001/3/30/entrez SP - 16168 EP - 76 JF - The Journal of biological chemistry JO - J Biol Chem VL - 276 IS - 19 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/11278619/Control_of_mitochondrial_redox_balance_and_cellular_defense_against_oxidative_damage_by_mitochondrial_NADP+_dependent_isocitrate_dehydrogenase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)32040-X DB - PRIME DP - Unbound Medicine ER -