The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to hypertrophy and aging

• Published in: Journal of molecular and cellular cardiology Vol. 52; no. 3; pp. 520 - 525
• Main Author: Sack, Michael N
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2012
• Subjects: Acetylation; Adaptation, Physiological; Aging - metabolism; Animals; Cardiac hypertrophy; Cardiomegaly - metabolism; Cardiovascular; Cyclophilin D; Enzyme Activation; Homeostasis; Humans; Lysine - metabolism; Mitochondria; Mitochondria, Heart - metabolism; Mitochondrial Proteins - metabolism; MnSOD; SIRT3; Sirtuin 3 - metabolism; Cyclophilin D; Tat-interactive protein 60; long chain acetyl-CoA dehydrogenase; histone acetyltransferase; PTM; post translational modification; aldehyde dehydrogenase 2; NMNAT; MPT; nicotinamide adenine dinucleotide; Mitochondria; CREB; ALDH2; cyclic AMP response element binding protein; NAMPT; reactive oxygen species; PGC-1; manganese superoxide dismutase; nicotinamide phosphoribosyltransferase; tricarboxylic acid; Tip60; mitochondrial permeability transition; Cardiac hypertrophy; Gcn5-related N-acetyltransferase; adenosine monophosphate kinase; histone deacetylase; NMN; SIRT3; NAD; peroxisome proliferator activated receptor gamma coactivator 1; TCA; MnSOD; ROS; AMPK; LCAD; HAT; GNAT; nicotinamide mononucleotide; HDAC; NMN adenyltransferase
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2011.11.004

Abstract Although acetyl-modification of protein lysine residues has been recognized for many decades, the appreciation that this post-translational modification is highly prevalent in mitochondria and plays a pivotal regulatory role in mitochondrial function has only become apparent since 2006. The classical biological stressors that modulate mitochondrial protein acetylation include alterations in caloric levels and redox signaling and the major enzyme orchestrating deacetylation is the mitochondrial enriched sirtuin SIRT3. Overall the action of SIRT3 modulates mitochondrial homeostasis and SIRT3 target proteins include mediators of energy metabolism and mitochondrial redox stress adaptive program proteins. Given these effects, it is not surprising that the role of SIRT3 has begun to be implicated in cardiac biology. This review gives a brief overview of sirtuin biology and then focuses on the role of the SIRT3 regulatory program in the control of cardiac hypertrophy and aging. This article is part of a Special Section entitled “Post-translational Modification.”