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(Circulation Research. 2009;105:830.)
© 2009 American Heart Association, Inc.

Review

The Emerging Characterization of Lysine Residue Deacetylation on the Modulation of Mitochondrial Function and Cardiovascular Biology

Zhongping Lu, Iain Scott, Bradley R. Webster, Michael N. Sack

From the Translational Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, Md.

Correspondence to Michael N. Sack, Bld 10-CRC, Room 5-3150, 10 Center Dr, MSC 1454, Bethesda, MD 20892-1454. E-mail sackm{at}nhlbi.nih.gov

This Review is the first article in a thematic series on Novel Posttranslational Modifications of Proteins and Their Cardiovascular Significance, which includes the following articles:

The Emerging Characterization of Lysine Residue Deacetylation on the Modulation of Mitochondrial Function and Cardiovascular Biology

S-Nitrosylation and Cardiovascular Signaling

S-Nitrosylation and Cardiac Ischemia

Glycosylation and Cardiovascular Signaling

Acetylation and Cardiovascular Signaling and Growth

Ubiquitination and Cardiovascular Signaling

Sumoylation and Regulation of Cardiac Gene Expression
Elizabeth Murphy Guest Editor

Abstract: There is emerging recognition of a novel fuel and redox sensing regulatory program that controls cellular adaptation via nonhistone protein lysine residue acetyl posttranslation modifications. This program functions in tissues with high energy demand and oxidative capacity and is highly enriched in the heart. Deacetylation is regulated by NAD⁺-dependent activation of the sirtuin family of proteins, whereas acetyltransferase modifications are controlled by less clearly delineated acetyltransferases. Subcellular localization specific protein targets of lysine-acetyl modification have been identified in the nucleus, cytoplasm, and mitochondria. Despite distinct subcellular localizations, these modifications appear, in large part, to modify mitochondrial properties including respiration, energy production, apoptosis, and antioxidant defenses. These mitochondrial regulatory programs are important in cardiovascular biology, although how protein acetyl modifications effects cardiovascular pathophysiology has not been extensively explored. This review will introduce the role of nonhistone protein lysine residue acetyl modifications, discuss their regulation and biochemistry and present the direct and indirect data implicating their involvement in the heart and vasculature.

Key Words: sirtuins • mitochondrial metabolism • apoptosis • redox stress • heart • vascular biology