Journal article
Exploring the electrostatic repulsion model in the role of Sirt3 in directing MnSOD acetylation status and enzymatic activity
Free radical biology & medicine, Vol.53(4), pp.828-833
08/15/2012
DOI: 10.1016/j.freeradbiomed.2012.06.020
PMCID: PMC3418453
PMID: 22732184
Abstract
Mitochondrial oxidative metabolism is the major site of ATP production as well as a significant source of reactive oxygen species (ROS) that can cause damage to critical biomolecules. It is well known that mitochondrial enzymes that scavenge ROS are targeted by stress responsive proteins to maintain the fidelity of mitochondrial function. Manganese superoxide dismutase (MnSOD) is a primary mitochondrial ROS scavenging enzyme, and in 1983 Irwin Fridovich proposed an elegant chemical mechanism/model whereby acetylation directs MnSOD enzymatic activity. He christened it the “electrostatic repulsion model.” However, the biochemical and genetic mechanism(s) determining how acetylation directs activity and the reasons behind the evolutionarily conserved need for several layers of transcriptional and posttranslational MnSOD regulation remain unknown. In this regard, we and others have shown that MnSOD is regulated, at least in part, by the deacetylation of specific conserved lysines in a reaction catalyzed by the mitochondrial sirtuin, Sirt3. We speculate that the regulation of MnSOD activity by lysine acetylation via an electrostatic repulsion mechanism is a conserved and critical aspect of MnSOD regulation necessary to maintain mitochondrial homeostasis.
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► MnSOD enzymatic activity is directed by lysine acetylation status. ► Sirt3 deacetylates MnSOD and alters enzymatic activity. ► Electrostatic Repulsion Model connects Sirt3 and MnSOD enzymatic activity.
Details
- Title: Subtitle
- Exploring the electrostatic repulsion model in the role of Sirt3 in directing MnSOD acetylation status and enzymatic activity
- Creators
- Yueming Zhu - Departments of Cancer Biology, Pediatrics, and Radiation Oncology, and Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USASeong-Hoon Park - Departments of Cancer Biology, Pediatrics, and Radiation Oncology, and Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USAOzkan Ozden - Departments of Cancer Biology, Pediatrics, and Radiation Oncology, and Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USAHyun-Seok Kim - Department of Life Science, College of Natural Science, Ewha Womans University, Seoul 127-750, KoreaHaiyan Jiang - Departments of Cancer Biology, Pediatrics, and Radiation Oncology, and Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USAAthanassios Vassilopoulos - Departments of Cancer Biology, Pediatrics, and Radiation Oncology, and Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USADouglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USADavid Gius - Departments of Cancer Biology, Pediatrics, and Radiation Oncology, and Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.53(4), pp.828-833
- DOI
- 10.1016/j.freeradbiomed.2012.06.020
- PMID
- 22732184
- PMCID
- PMC3418453
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Grant note
- name: D.G., award: NCI-1R01CA152601-01, 1R01CA152799-01A1; name: D.R.S., award: R01CA133114, DE-SC0000830, P30CA086862
- Language
- English
- Date published
- 08/15/2012
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984047770902771
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