Exploring the electrostatic repulsion model in the role of Sirt3 in directing MnSOD acetylation status and enzymatic activity

Yueming Zhu, Seong Hoon Park, Ozkan Ozden, Hyun Seok Kim, Haiyan Jiang, Athanassios Vassilopoulos, Douglas R. Spitz, David Gius

Research output: Contribution to journalReview articlepeer-review

51 Scopus citations


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.

Original languageEnglish
Pages (from-to)828-833
Number of pages6
JournalFree Radical Biology and Medicine
Issue number4
StatePublished - 15 Aug 2012

Bibliographical note

Funding Information:
D.G. is supported by NCI-1R01CA152601-01 , 1R01CA152799-01A1 , BC093803 from the DOD, and a Hirshberg Foundation for Pancreatic Cancer Research Seed Grant Award. D.R.S. is supported by R01CA133114 , DE-SC0000830 , and P30CA086862 . We thank Melissa Stauffer of Scientific Editing Solutions for editing the manuscript.


  • Acetylation
  • Acetylome
  • Electrostatic repulsion model
  • Metabolic homeostasis
  • Metabolism
  • Mitochondria
  • MnSOD
  • ROS
  • Sirt3
  • Sirtuins


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