Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2.
Reads0
Chats0
TLDR
The findings show that a mammalian sirtuin directly controls the activity of a metabolic enzyme by means of reversible lysine acetylation, and highlights the conservation of a metabolism regulatory pathway from bacteria to humans.Abstract:
We report that human acetyl-CoA synthetase 2 (AceCS2) is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at Lys-642 in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys-642 both in vitro and in vivo. Deacetylation of AceCS2 by SIRT3 activates the acetyl-CoA synthetase activity of AceCS2. This report identifies the first acetylated substrate protein of SIRT3. Our findings show that a mammalian sirtuin directly controls the activity of a metabolic enzyme by means of reversible lysine acetylation. Because the activity of a bacterial ortholog of AceCS2, called ACS, is controlled via deacetylation by a bacterial sirtuin protein, our observation highlights the conservation of a metabolic regulatory pathway from bacteria to humans.read more
Citations
More filters
Journal ArticleDOI
Mammalian sirtuins: biological insights and disease relevance.
TL;DR: There have been major advances in the understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span, and the challenges that will confront the field in the coming years are discussed.
Journal ArticleDOI
Sirtuins in mammals: insights into their biological function
Shaday Michan,David A. Sinclair +1 more
TL;DR: The current understanding of the biological function of the seven mammalian sirtuins, SIRT1-7, is described and their potential as mediators of caloric restriction and as pharmacological targets to delay and treat human age-related diseases are discussed.
Journal ArticleDOI
SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Matthew D. Hirschey,Tadahiro Shimazu,Tadahiro Shimazu,Eric S. Goetzman,Enxuan Jing,Bjoern Schwer,Bjoern Schwer,Bjoern Schwer,David B. Lombard,Carrie A. Grueter,Charles A. Harris,Sudha B. Biddinger,Olga Ilkayeva,Robert Stevens,Yu Li,Asish K. Saha,Neil B. Ruderman,James R. Bain,Christopher B. Newgard,Robert V. Farese,Frederick W. Alt,C. Ronald Kahn,Eric Verdin,Eric Verdin +23 more
TL;DR: It is demonstrated that SIRT3 modulates mitochondrial intermediary metabolism and fatty-acid use during fasting and acetylation is identified as a novel regulatory mechanism for mitochondrial fatty- acid oxidation.
Journal ArticleDOI
Recent progress in the biology and physiology of sirtuins
TL;DR: The recent progress in sirtuin biology, the role these proteins have in various age-related diseases and the tantalizing notion that the activity of this family of enzymes somehow regulates how long the authors live are reviewed.
Journal ArticleDOI
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
TL;DR: Recent findings demonstrating the role of mammalian sirtuins as regulators of physiology, calorie restriction, and aging sharpen the understanding of sirtUins as potential pharmacological targets to treat the major diseases of aging.
References
More filters
Journal ArticleDOI
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products
TL;DR: A simple and highly efficient method to disrupt chromosomal genes in Escherichia coli in which PCR primers provide the homology to the targeted gene(s), which should be widely useful, especially in genome analysis of E. coli and other bacteria.
Journal ArticleDOI
Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked
Jie Yang,Xuesong Liu,Xuesong Liu,Kapil N. Bhalla,Caryn Naekyung Kim,Ana Maria Ibrado,Jiyang Cai,Tsung I. Peng,Dean P. Jones,Xiaodong Wang,Xiaodong Wang +10 more
TL;DR: One possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria, which is normally located in the mitochondrial intermembrane space.
Journal ArticleDOI
The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms
TL;DR: It is shown that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining, and increasing the gene dosage extends the life span in wild-type cells.
Journal ArticleDOI
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
TL;DR: In this paper, the lifespan of C. elegans strains containing duplications of chromosomal regions was surveyed and it was shown that a duplication containing sir-2.1-the SIR2 gene most homologous to yeast-confers a lifespan that is extended by up to 50%.
Journal ArticleDOI
Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae
TL;DR: These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD, the oxidized form of nicotinamide adenine dinucleotide.
Related Papers (5)
SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Matthew D. Hirschey,Tadahiro Shimazu,Tadahiro Shimazu,Eric S. Goetzman,Enxuan Jing,Bjoern Schwer,Bjoern Schwer,Bjoern Schwer,David B. Lombard,Carrie A. Grueter,Charles A. Harris,Sudha B. Biddinger,Olga Ilkayeva,Robert Stevens,Yu Li,Asish K. Saha,Neil B. Ruderman,James R. Bain,Christopher B. Newgard,Robert V. Farese,Frederick W. Alt,C. Ronald Kahn,Eric Verdin,Eric Verdin +23 more