title: Mitochondrion as a Target for Heart Failure Therapy- Role of Protein Lysine Acetylation.
abstract: Heart failure is a leading cause of death worldwide. Despite medical advances, the dismal prognosis of heart failure has not been improved. The heart is a high energy-demanding organ. Impairments of cardiac energy metabolism and mitochondrial function are intricately linked to cardiac dysfunction. Mitochondrial dysfunction contributes to impaired myocardial energetics and increased oxidative stress in heart failure, and the opening of mitochondrial permeability transition pore triggers cell death and myocardial remodeling. Therefore, there has been growing interest in targeting mitochondria and metabolism for heart failure therapy. Recent developments suggest that mitochondrial protein lysine acetylation modulates the sensitivity of the heart to stress and hence the propensity to heart failure. This article reviews the role of mitochondrial dysfunction in heart failure, with a special emphasis on the regulation of the nicotinamide adenine dinucleotide (NAD(+)/NADH) ratio and sirtuin-dependent lysine acetylation by mitochondrial function. Strategies for targeting NAD(+)-sensitive mechanisms in order to intervene in protein lysine acetylation and, thereby, improve stress tolerance, are described, and their usefulness in heart failure therapy is discussed.
authors.affiliation: Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington.
authors.forename: Chi Fung
authors.initials: CF
authors.lastname: Lee
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
mesh_terms: D000107:Acetylation; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D037761:Sirtuins; D008239:Lysine