Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 53, Issue 4, Pages 828-833Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2012.06.020
Keywords
Electrostatic repulsion model; MnSOD; Sirt3; Sirtuins; Metabolism; Mitochondria; ROS; Acetylation; Acetylome; Metabolic homeostasis
Funding
- DOD [BC093803]
- Hirshberg Foundation for Pancreatic Cancer Research Seed Grant Award
- [NCI-1R01CA152601-01]
- [1R01CA152799-01A1]
- [R01CA133114]
- [DE-SC0000830]
- [P30CA086862]
Ask authors/readers for more resources
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 mitochondria! 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. (C) 2012 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available