SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense
© 2016 The Authors..
Excess in mitochondrial reactive oxygen species (ROS) is considered as a major cause of cellular oxidative stress. NADPH, the main intracellular reductant, has a key role in keeping glutathione in its reduced form GSH, which scavenges ROS and thus protects the cell from oxidative damage. Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes. Moreover, we show that knockdown or knockout of SIRT5 leads to high levels of cellular ROS SIRT5 inactivation leads to the inhibition of IDH2 and G6PD, thereby decreasing NADPH production, lowering GSH, impairing the ability to scavenge ROS, and increasing cellular susceptibility to oxidative stress. Our study uncovers a SIRT5-dependent mechanism that regulates cellular NADPH homeostasis and redox potential by promoting IDH2 desuccinylation and G6PD deglutarylation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
EMBO reports - 17(2016), 6 vom: 26. Juni, Seite 811-22 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Lisha [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.08.2017 Date Revised 12.08.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.15252/embr.201541643 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM259732370 |
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| 100 | 1 | |a Zhou, Lisha |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense |
| 264 | 1 | |c 2016 | |
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| 500 | |a Date Completed 15.08.2017 | ||
| 500 | |a Date Revised 12.08.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2016 The Authors. | ||
| 520 | |a Excess in mitochondrial reactive oxygen species (ROS) is considered as a major cause of cellular oxidative stress. NADPH, the main intracellular reductant, has a key role in keeping glutathione in its reduced form GSH, which scavenges ROS and thus protects the cell from oxidative damage. Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes. Moreover, we show that knockdown or knockout of SIRT5 leads to high levels of cellular ROS SIRT5 inactivation leads to the inhibition of IDH2 and G6PD, thereby decreasing NADPH production, lowering GSH, impairing the ability to scavenge ROS, and increasing cellular susceptibility to oxidative stress. Our study uncovers a SIRT5-dependent mechanism that regulates cellular NADPH homeostasis and redox potential by promoting IDH2 desuccinylation and G6PD deglutarylation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a NADPH | |
| 650 | 4 | |a SIRT5 | |
| 650 | 4 | |a glutarylation | |
| 650 | 4 | |a oxidative stress | |
| 650 | 4 | |a succinylation | |
| 650 | 7 | |a Antioxidants |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a NADP |2 NLM | |
| 650 | 7 | |a 53-59-8 |2 NLM | |
| 650 | 7 | |a IDH2 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.1.1.41 |2 NLM | |
| 650 | 7 | |a Isocitrate Dehydrogenase |2 NLM | |
| 650 | 7 | |a EC 1.1.1.41 |2 NLM | |
| 650 | 7 | |a Glucosephosphate Dehydrogenase |2 NLM | |
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| 650 | 7 | |a SIRT5 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.5.1.- |2 NLM | |
| 650 | 7 | |a Sirtuins |2 NLM | |
| 650 | 7 | |a EC 3.5.1.- |2 NLM | |
| 650 | 7 | |a Glutathione |2 NLM | |
| 650 | 7 | |a GAN16C9B8O |2 NLM | |
| 700 | 1 | |a Wang, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Renqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiufei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Mengli |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shiwen |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Kun-Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Pengyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Hongxiu |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Dan |e verfasserin |4 aut | |
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