Mechanism Of Protein Acetylation In Mitochondria

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Mechanism of Protein Acetylation in Mitochondria

Author : Josue Baeza
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (17 download)

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Book Synopsis Mechanism of Protein Acetylation in Mitochondria by : Josue Baeza

Download or read book Mechanism of Protein Acetylation in Mitochondria written by Josue Baeza and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Reversible N-[epsilon]-acetylation has emerged as a widespread and regulatory modification throughout the cell. First identified on N-terminal histone tails over 50 years ago, acetylation has now been identified on over 36,000 lysine sites on organisms ranging from bacteria to mammals, highlighting the strong, conserved role for this modification. Acetylation is controlled by the opposing action of lysine acetyltransferases and deacetylases and recent evidence supports a role for nonenzymatic acetylation. Lysine acetylation influences many biochemical processes including: protein-protein and protein-DNA interactions, stability, cellular localization and enzymatic activity, which is thought to arise from neutralization of the positive charge on lysine residues at neutral pH. In mitochondria, acetylation generally acts as an inhibitory modification, altering protein interactions, lowered enzymatic activity and mislocalization of mitochondrial proteins. In this case, acetylation acts as a rheostat, modulating the degree of a biochemical process. Therefore, knowing the fraction of the protein that is modified, or stoichiometry, would provide critical information for understanding the regulatory effects of lysine acetylation. The mechanism of mitochondrial protein acetylation remains unknown. While there is a wealth of data supporting a dynamic and regulatory role for acetylation within mitochondria, there is very little evidence for an enzyme-catalyzed reaction. However, the conditions of the mitochondrial matrix: elevated acetyl-CoA levels and alkaline pH, raise the possibility that lysine acetylation can occur nonenzymatically. Throughout my thesis research, I have utilized chemical, biochemical, proteomic, and cellular studies to characterize protein acetylation. Specifically, I developed a mass spectrometry based approach to directly quantify lysine acetylation stoichiometry at the proteome-wide scale. Using this newly developed method, I measured the second order rate constants of nonenzymatic lysine acetylation using mitochondrial and non-mitochondrial proteins, highlighting the wide range of reactivities. The characterization of nonenzymatic rates of native protein demonstrates that the uncatalyzed reaction can account for the levels of acetylation in vivo. I also provide evidence that the majority of mitochondrial acetylation occurs within the mitochondria. Chapter 1 introduces lysine acetylation, the various processes controlling cellular levels including enzymatic and nonenzymatic, and why quantifying acetylation stoichiometry is needed. Chapter 2 discusses the mass spectrometry based method used for quantifying stoichiometry and its application in the model system, Escherichia coli. In chapter 3, I quantify the rates of nonenzymatic acetylation using a panel of mitochondrial and nonmitochondrial proteins, which highlights, for the first time, the wide range of lysine reactivities on native proteins. I then utilize an optimized version of the stoichiometry method to query mammalian lysine acetylation stoichiometry, revealing the wide distribution of acetylation across the cell. Conclusions, ongoing work, and future directions are presented in Chapter 5.

Reversible Protein Acetylation in the Mitochondria

Author :
Publisher :
ISBN 13 :
Total Pages : 270 pages
Book Rating : 4.:/5 (888 download)

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Download or read book Reversible Protein Acetylation in the Mitochondria written by and published by . This book was released on 2014 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein acetylation has emerged as a major post-translational modification and accumulating evidence indicates that lysine acetylation is a prevalent regulatory mechanism of numerous cellular processes. Mitochondrial proteins, including metabolic enzymes, are among the most highly acetylated and are dynamically altered in response to nutritional status. The mitochondrial nicotinamide adenine dinucleotide dependent deacetylase Sirtuin 3 (SIRT3) is implicated as a possible regulator of the cellular adaptation to nutrient variation and directly deacetylates and regulates the function of proteins involved in lipid metabolism, energy production, and the antioxidant response system. Mitochondrial function has been linked with aging and age-related disease. SIRT3 may play a major role in the maintenance of healthy mitochondria and act as a key molecular regulator of the lifespan benefits of caloric restriction, fasting, and exercise. SIRT3 is postulated to be the main, if only, mitochondrial protein deacetylase, but the extent of its capacity to modulate mitochondrial processes remains unclear. While numerous post-translational modifications exist in the mitochondria, much remains to be understood about the enzymes that add and remove these chemical marks, how this serves to regulate protein function, and how these modifications vary in response to both acute and chronic alterations in nutrient availability. Employing biochemistry and systems biology to test defined hypotheses will allow for exploration of a number of unexplored and unknown questions in the field of mitochondrial biology and will further elucidate the role of mitochondria in aging and disease. This thesis describes the characterization of physiological, site-specific alterations in lysine acetylation in the mitochondria. Using mouse models, quantitative proteomics, detailed biochemistry, and cell culture systems this work stands to elucidate mechanistic details of the regulatory role of protein acetylation.

Influence of HINT-2 on Mitochondrial Protein Acetylation

Author : Raviprasadh Rajasekaran
Publisher :
ISBN 13 :
Total Pages : 169 pages
Book Rating : 4.:/5 (112 download)

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Book Synopsis Influence of HINT-2 on Mitochondrial Protein Acetylation by : Raviprasadh Rajasekaran

Download or read book Influence of HINT-2 on Mitochondrial Protein Acetylation written by Raviprasadh Rajasekaran and published by . This book was released on 2018 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt:

The Organic Chemistry of Biological Pathways

Author : John McMurry
Publisher : Roberts and Company Publishers
ISBN 13 : 9780974707716
Total Pages : 524 pages
Book Rating : 4.7/5 (77 download)

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Book Synopsis The Organic Chemistry of Biological Pathways by : John McMurry

Download or read book The Organic Chemistry of Biological Pathways written by John McMurry and published by Roberts and Company Publishers. This book was released on 2005 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt: Intended for advanced undergraduates and graduate students in all areas of biochemistry, The Organic Chemistry of Biological Pathways provides an accurate treatment of the major biochemical pathways from the perspective of mechanistic organic chemistry.

Mechanism and Dynamics of Acyl-CoA Mediated Protein Lysine Acylation in Mitochondria

Author : Zeljko Simic
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (962 download)

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Book Synopsis Mechanism and Dynamics of Acyl-CoA Mediated Protein Lysine Acylation in Mitochondria by : Zeljko Simic

Download or read book Mechanism and Dynamics of Acyl-CoA Mediated Protein Lysine Acylation in Mitochondria written by Zeljko Simic and published by . This book was released on 2016* with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria represent cellular organelles with a high level of acetylated proteins in comparison to other cellular compartments but mitochondrial residential lysine acetyltransferases have not been recognized. Here we show that acetylation, as well as other acylations are spontaneous processes that depend on pH value, acyl-CoA concentration and the chemical nature of the acyl residue. In the case of short peptide substrate derived from carbamoyl phosphate synthetase 1, dicarboxylic acyl groups show highest level of reactivity. Reactivities of the CoA-thioesters decrease with extending the acyl chain. These results were confirmed by using the protein substrate cyclophilin A. Deacylation experiments revealed that SIRT3 exhibits deacetylase activity but is not able to remove any of the succinyl group from cyclophilinA, whereas SIRT5 is an efficient protein desuccinylase. Considering that we have not found convincing evidence about existence of mitochondrial lysine acetyltransferase so far, it leads to conclusion that acylation landscape on the lysine residues might largely depend on the enzymatic activities of sirtuins and availability and/or reactivity of certain acyl-CoA thioesters.

Mechanism and Dynamics of Acyl-CoA Mediated Protein Lysine Acylation in Mitochondria

Author : Zeljko Simic
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (962 download)

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Book Synopsis Mechanism and Dynamics of Acyl-CoA Mediated Protein Lysine Acylation in Mitochondria by : Zeljko Simic

Download or read book Mechanism and Dynamics of Acyl-CoA Mediated Protein Lysine Acylation in Mitochondria written by Zeljko Simic and published by . This book was released on 2016* with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria represent cellular organelles with a high level of acetylated proteins in comparison to other cellular compartments but mitochondrial residential lysine acetyltransferases have not been recognized. Here we show that acetylation, as well as other acylations are spontaneous processes that depend on pH value, acyl-CoA concentration and the chemical nature of the acyl residue. In the case of short peptide substrate derived from carbamoyl phosphate synthetase 1, dicarboxylic acyl groups show highest level of reactivity. Reactivities of the CoA-thioesters decrease with extending the acyl chain. These results were confirmed by using the protein substrate cyclophilin A. Deacylation experiments revealed that SIRT3 exhibits deacetylase activity but is not able to remove any of the succinyl group from cyclophilinA, whereas SIRT5 is an efficient protein desuccinylase. Considering that we have not found convincing evidence about existence of mitochondrial lysine acetyltransferase so far, it leads to conclusion that acylation landscape on the lysine residues might largely depend on the enzymatic activities of sirtuins and availability and/or reactivity of certain acyl-CoA thioesters.

Investigating the Regulatory Mechanisms Driving Dynamic Protein Acetylation in the Cell

Author : Alexis Jo Lawton (Ph.D.)
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (139 download)

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Book Synopsis Investigating the Regulatory Mechanisms Driving Dynamic Protein Acetylation in the Cell by : Alexis Jo Lawton (Ph.D.)

Download or read book Investigating the Regulatory Mechanisms Driving Dynamic Protein Acetylation in the Cell written by Alexis Jo Lawton (Ph.D.) and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Reversible protein acetylation is a widespread, regulatory modification that was first discovered on histone proteins, but since has been described throughout the cell in major subcellular compartments. Several functional roles of lysine acetylation have been described including regulating enzymatic activity, protein-protein interactions, protein-DNA interactions, protein stability, and subcellular localization. With the improvements in mass spectrometry technologies, the number of identified acetylated sites has grown exponentially creating a new challenge to determine which sites are functional versus spurious. Furthermore, studies investigating the mechanisms regulating protein acetylation have primarily focused on histone acetylation, but how they may regulate non-histone protein acetylation has not been fully understood. Of importance, one of the main mechanisms through which acetylation may be regulated is through changes in the availability of acetyl-CoA. Since most acetyltransferases, including p300/CBP, have a Km near the estimated cellular concentrations of acetyl-CoA, manipulating concentrations of the substrate through activation of its production can have major effects on the levels of acetylation. Several studies have investigated the effect of knockdowns of acetyl-CoA generating enzymes (such as ACLY or ACSS2), however, few studies have measured the effects on non-histone protein acetylation. My research uses two main approaches to respond to these challenges in the field: 1) a robust, mass spectrometry method to quantify acetylation stoichiometry across the proteome, and 2) investigating dynamics of acetylation in response to changes in acetyl-CoA availability. Understanding both stoichiometry and dynamic responses during cellular stimulation are key features of interrogating the role of protein acetylation at a site- and protein-specific level. My research aims to understand the cellular mechanisms that are controlling dynamic acetylation in response to metabolic changes in acetyl Coenzyme A (acetyl-CoA) availability and production.Here, I examine the dynamics of global protein acetylation and the mechanisms regulating growth-factor stimulated dynamics, with a particular focus on how metabolism and the production and availability of acetyl-CoA is a major regulator of protein acetylation. Chapter 1 introduces protein acetylation and discusses the field's current understanding of acetylation functions, the quantitative techniques for investigating global non-histone protein acetylation, and the mechanisms involved in regulating protein acetylation. Chapter 2 presents an updated method for quantifying lysine acetylation stoichiometry and applies this method to identify serum-stimulated protein acetylation dynamics. Chapter 3 presents an in-progress project that examines the key regulatory nodes controlling growth-factor stimulated acetylation, including the kinase AKT, acetyl-CoA production through ACLY, and citrate export by SLC25A1. Chapter 4 presents the ongoing experiments and future directions for these projects. My thesis work has also allowed me to be a part of some critical collaborations that have investigated the connection between metabolism, acetyl-CoA availability, and protein acetylation in several interesting mouse models. My contributions and our key findings are presented in the Appendixes of this thesis. Appendix 1 investigates the effect of the dysregulation of the ER-localized acetyl-CoA transporter, AT-1, on protein acetylation. Appendix 2 investigates the effect of increased flux of citrate into the cytoplasm and nucleus through overexpression models of the extracellular membrane citrate transporter, SLC13A5, and the mitochondrial citrate transporter, SLC25A1, and their effect on protein acetylation. Appendix 3 investigates the effect of age, diet, and the loss of the mitochondrial localized deacetylase, SIRT3, on mitochondrial protein acetylation. Lastly, Appendix 4 examines the effects of the loss of individual ER-localized acetyltransferases, ATase1 and ATase2, on secretory pathway protein acetylation.

Identification and Characterization of Altered Mitochondrial Protein Acetylation in Friedreich's Ataxia Cardiomyopathy

Author : Gregory Randall Wagner
Publisher :
ISBN 13 :
Total Pages : 252 pages
Book Rating : 4.:/5 (875 download)

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Book Synopsis Identification and Characterization of Altered Mitochondrial Protein Acetylation in Friedreich's Ataxia Cardiomyopathy by : Gregory Randall Wagner

Download or read book Identification and Characterization of Altered Mitochondrial Protein Acetylation in Friedreich's Ataxia Cardiomyopathy written by Gregory Randall Wagner and published by . This book was released on 2013 with total page 252 pages. Available in PDF, EPUB and Kindle. Book excerpt: Friedreich's Ataxia (FRDA) is a rare and poorly understood autosomal recessive disease caused by a pathological deficiency of the mitochondrial protein frataxin. Patients suffer neurodegeneration, ataxia, diabetes, and heart failure. In an effort to understand the mechanisms of heart failure in FRDA, we investigated the role of the protein modification acetylation, which is highly abundant on mitochondrial proteins and has been implicated in regulating intermediary metabolism. Using mouse models of FRDA, we found that cardiac frataxin deficiency causes progressive hyperacetylation of mitochondrial proteins which is correlated with loss of respiratory chain subunits and an altered mitochondrial redox state. Mitochondrial protein hyperacetylation could be reversed by the mitochondria-localized deacetylase SIRT3 in vitro, suggesting a defect in endogenous SIRT3 activity. Consistently, frataxin-deficient cardiac mitochondria showed significantly decreased rates of fatty acid oxidation and complete oxidation to carbon dioxide. However, the degree of protein hyperacetylation in FRDA could not be fully explained by SIRT3 loss. Our data suggested that intermediary metabolites and perhaps acetyl-CoA, which is required for protein acetylation, are accumulating in frataxin-deficient mitochondria. Upon testing the hypothesis that mitochondrial protein acetylation is non-enzymatic, we found that the minimal chemical conditions of the mitochondrial matrix are sufficient to cause widespread non-enzymatic protein acetylation in vitro. These data suggest that mitochondrial protein hyperacetylation in FRDA cardiomyopathy mediates progressive post-translational suppression of mitochondrial oxidative pathways which is caused by a combination of SIRT3 deficiency and, likely, an accumulation of unoxidized acetyl-CoA capable of initiating non-enzymatic protein acetylation. These findings provide novel insight into the mechanisms underlying a poorly understood and fatal cardiomyopathy and highlight a fundamental biochemical mechanism that had been previously overlooked in biological systems.

Investigating the Regulatory Mechanisms Driving Dynamic Protein Acetylation in the Cell

Author : Alexis Jo Lawton (Ph.D.)
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (138 download)

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Book Synopsis Investigating the Regulatory Mechanisms Driving Dynamic Protein Acetylation in the Cell by : Alexis Jo Lawton (Ph.D.)

Protein Targeting to Mitochondria

Author : F.U. Hartl
Publisher : Elsevier
ISBN 13 : 0080877001
Total Pages : 377 pages
Book Rating : 4.0/5 (88 download)

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Book Synopsis Protein Targeting to Mitochondria by : F.U. Hartl

Download or read book Protein Targeting to Mitochondria written by F.U. Hartl and published by Elsevier. This book was released on 1997-02-24 with total page 377 pages. Available in PDF, EPUB and Kindle. Book excerpt: A large number of newly-synthesized polypeptides must cross one or several intracellular membranes to reach their functional locations in the eukaryotic cell. The mechanisms of protein trafficking, in particular the post-translational targeting and membrane translocation of proteins, are of fundamental biological importance and are the focus of intensive research world-wide. For more than 15 years, mitochondria have served as the paradigm organelle system to study these processes. Although key questions, such as how precisely proteins cross a membrane, still remain to be answered, exciting progress has been made in understanding the basic pathways of protein import into mitochondria and the components involved. In addition to a fascinating richness and complexity in detail, the analysis of mitochondrial protein import has revealed mechanistic principles of general significance: Major discoveries include the demonstration of the requirement of an unfolded state for translocation and of the essential role of molecular chaperones on both sides of the membranes in maintaining a translocation-competent conformation and in protein folding after import. It is becoming clear how a polypeptide chain is "reeled" across the membrane in an ATP-dependent process by the functional cooperation of membrane proteins, presumably constituting part of a transmembrane channel, with peripheral components at the trans-side of the membrane.In this volume, eminent experts in the field take the time to review the central aspects of mitochondrial biogenesis. The logical order of the 16 chapters is determined by the sequence of steps during protein import, starting with the events taking place in the cytosol, followed by the recognition of targeting signals, the translocation of precursor proteins across the outer and inner membranes, their proteolytic processing and intramitochondrial sorting, and finally their folding and oligomeric assembly. In addition, the mechanisms involved in the export of mitochondrially encoded proteins as well as recent advances in understanding the division and inheritance of mitochondria will be discussed.

Protein Modificomics

Author : Tanveer Ali Dar
Publisher : Academic Press
ISBN 13 : 9780128119136
Total Pages : 0 pages
Book Rating : 4.1/5 (191 download)

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Book Synopsis Protein Modificomics by : Tanveer Ali Dar

Download or read book Protein Modificomics written by Tanveer Ali Dar and published by Academic Press. This book was released on 2019-05-21 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein Modificomics: From Modifications to Clinical Perspectives comprehensively deals with all of the most recent aspects of post-translational modification (PTM) of proteins, including discussions on diseases involving PTMs, such as Alzheimer's, Huntington's, X-linked spinal muscular atrophy-2, aneurysmal bone cyst, angelman syndrome and OFC10. The book also discusses the role PTMs play in plant physiology and the production of medicinally important primary and secondary metabolites. The understanding of PTMs in plants helps us enhance the production of these metabolites without greatly altering the genome, providing robust eukaryotic systems for the production and isolation of desired products without considerable downstream and isolation processes.

Co- and Post-Translational Modifications of Therapeutic Antibodies and Proteins

Author : T. Shantha Raju
Publisher : John Wiley & Sons
ISBN 13 : 111905334X
Total Pages : 304 pages
Book Rating : 4.1/5 (19 download)

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Book Synopsis Co- and Post-Translational Modifications of Therapeutic Antibodies and Proteins by : T. Shantha Raju

Download or read book Co- and Post-Translational Modifications of Therapeutic Antibodies and Proteins written by T. Shantha Raju and published by John Wiley & Sons. This book was released on 2019-03-15 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: A Comprehensive Guide to Crucial Attributes of Therapeutic Proteins in Biological Pharmaceuticals With this book, Dr. Raju offers a valuable resource for professionals involved in research and development of biopharmaceutical and biosimilar drugs. This is a highly relevant work, as medical practitioners have increasingly turned to biopharmaceutical medicines in their search for safe and reliable treatments for complex diseases, while pharmaceutical researchers seek to expand the availability of biopharmaceuticals and create more affordable biosimilar alternatives. Readers receive a thorough overview of the major co-translational modifications (CTMs) and post-translational modifications (PTMs) of therapeutic proteins relevant to the development of biotherapeutics. The majority of chapters detail individual CTMs and PTMs that may affect the physicochemical, biochemical, biological, pharmacokinetic, immunological, toxicological etc. properties of proteins. In addition, readers are guided on the methodology necessary to analyze and characterize these modifications. Thus, readers gain not only an understanding of CTMs/PTMs, but also the ability to design and assess their own structure-function studies for experimental molecules. Specific features and topics include: Discussion of the research behind and expansion of biopharmaceuticals Twenty chapters detailing relevant CTMs and PTMs of proteins, such as glycosylation, oxidation, phosphorylation, methylation, proteolysis, etc. Each chapter offers an introduction and guide to the mechanisms and biological significance of an individual CTM or PTM, including practical guidance for experiment design and analysis An appendix of biologic pharmaceuticals currently on the market, along with an assessment of their PTMs and overall safety and efficacy This volume will prove a key reference on the shelves of industry and academic researchers involved in the study and development of biochemistry, molecular biology, biopharmaceuticals and proteins in medicine, particularly as biopharmaceuticals and biosimilars become ever more prominent tools in the field of healthcare.

Introduction to Epigenetics

Author : Renato Paro
Publisher : Springer Nature
ISBN 13 : 3030686701
Total Pages : 215 pages
Book Rating : 4.0/5 (36 download)

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Book Synopsis Introduction to Epigenetics by : Renato Paro

Download or read book Introduction to Epigenetics written by Renato Paro and published by Springer Nature. This book was released on 2021-03-23 with total page 215 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease

Intermediary Metabolism

Author : Otto Hoffmann-Ostenhof
Publisher : Van Nostrand Reinhold Company
ISBN 13 :
Total Pages : 522 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Intermediary Metabolism by : Otto Hoffmann-Ostenhof

Download or read book Intermediary Metabolism written by Otto Hoffmann-Ostenhof and published by Van Nostrand Reinhold Company. This book was released on 1987 with total page 522 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Impact of Dynamic Post-translational Modifications on the Activities of Mitochondrial Proteins

Author : Amelia J. Nestler
Publisher :
ISBN 13 :
Total Pages : 328 pages
Book Rating : 4.:/5 (11 download)

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Book Synopsis Impact of Dynamic Post-translational Modifications on the Activities of Mitochondrial Proteins by : Amelia J. Nestler

Download or read book Impact of Dynamic Post-translational Modifications on the Activities of Mitochondrial Proteins written by Amelia J. Nestler and published by . This book was released on 2015 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria are dynamic organelles that control a diverse array of metabolic processes and must adapt to changes in nutrient availability. Understanding the mechanisms driving these adaptations promises to help us understand metabolic disease. One mechanism is via post-translational modifications (PTMs) on mitochondrial proteins. While it is established that PTMs can alter protein function, few examples exist where we have defined the specific functional changes, the mechanisms for these changes, and the relevant biological conditions. In my research, I have expanded our understanding of how the mitochondrial acetylome changes during alterations in nutrient availability, and how PTMs impact the activity of two enzymes: acetyl-CoA acetyltransferase 1 (Acat1) and dehydrogenase/reductase family member 4 (Dhrs4). In Chapter 1, I review our current knowledge relating PTMs and mitochondrial function and discuss innovative tools for studying them. This research is the foundation for my studies on acetylome changes and on the impact and mechanism of PTM regulation on specific enzymes. In Chapter 2, I explored changes to the mitochondrial acetylome in response to acute and chronic changes in nutrient availability. Using quantitative mass spectrometry, we determined changes in relative acetyl occupancy for thousands of acetylation sites. I discuss the overall state of the acetylome as well as the identification of potential regulatory acetylation sites. I demonstrated that acetylation of Acat1, an enzyme central to three metabolic pathways, at K260 and K265 decreases activity by disrupting the binding of the necessary coenzyme A (CoA) cofactor. In Chapter 3, I examined the impact of both lysine acetylation and serine phosphorylation on Dhrs4, and then proceed to explore the in vivo function of this mischaracterized enzyme. Abundance of proximal K217 acetylation and S221 phosphorylation both increase with obesity, and I determined that both modifications inhibit the activity of Dhrs4. I generated Dhrs4 knockout cell lines and discovered that it plays a central role in lipid metabolism. Finally, in Chapter 4 & 5, I conclude my research and propose future studies for exploring the regulatory role of PTMs in mitochondria. Innovative techniques currently under development form a robust system for discovering the biological importance of PTMs.

Regulatory Mechanisms for Protein Synthesis in Mammalian Cells

Author : Anthony Gordan San Pietro
Publisher :
ISBN 13 :
Total Pages : 504 pages
Book Rating : 4.:/5 (89 download)

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Book Synopsis Regulatory Mechanisms for Protein Synthesis in Mammalian Cells by : Anthony Gordan San Pietro

Download or read book Regulatory Mechanisms for Protein Synthesis in Mammalian Cells written by Anthony Gordan San Pietro and published by . This book was released on 1968 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Reversible Protein Acetylation

Author : Gregory R. Bock
Publisher : John Wiley & Sons
ISBN 13 : 0470862629
Total Pages : 310 pages
Book Rating : 4.4/5 (78 download)

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Book Synopsis Reversible Protein Acetylation by : Gregory R. Bock

Download or read book Reversible Protein Acetylation written by Gregory R. Bock and published by John Wiley & Sons. This book was released on 2004-07-16 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive review of recent work on chromatin and non-histone proteins, this book arises from the interactions of a multidisciplinary group of scientists involved in the study of acetylation. This area of research opens up new and exciting possibilities for drug design, and so the final chapters in the book examine some of the potential applications in the treatment of various diseases.