Exploring the electrostatic repulsion model in the role of Sirt3 in directing MnSOD acetylation status and enzymatic activity.
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.
Department of Cancer Biology, and Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
Yueming
Y
Zhu
Seong-Hoon
SH
Park
Ozkan
O
Ozden
Hyun-Seok
HS
Kim
Haiyan
H
Jiang
Athanassios
A
Vassilopoulos
Douglas R
DR
Spitz
David
D
Gius
D000107:Acetylation; D000818:Animals; D004563:Electrochemistry; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D056566:Sirtuin 3 / Q000737:chemistry / Q000502:physiology*; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*
D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; C466093:SIRT3 protein, human; D056566:Sirtuin 3