The role of protein acetylation in regulating mitochondrial fusion and fission

2021 ◽  
Author(s):  
Golam M. Uddin ◽  
Rafa Abbas ◽  
Timothy E. Shutt
Keyword(s):  
Mitochondrial Function ◽  
Regulatory Mechanism ◽  
Mitochondrial Fusion ◽  
Dynamic Processes ◽  
Protein Acetylation ◽  
Post Translational Modification ◽  
Acetylation Status

The dynamic processes of mitochondrial fusion and fission determine the shape of mitochondria, which can range from individual fragments to a hyperfused network, and influence mitochondrial function. Changes in mitochondrial shape can occur rapidly, allowing mitochondria to adapt to specific cues and changing cellular demands. Here, we will review what is known about how key proteins required for mitochondrial fusion and fission are regulated by their acetylation status, with acetylation promoting fission and deacetylation enhancing fusion. In particular, we will examine the roles of NAD+ dependant sirtuin deacetylases, which mediate mitochondrial acetylation, and how this post-translational modification provides an exquisite regulatory mechanism to co-ordinate mitochondrial function with metabolic demands of the cell.

scholarly journals Evolution of molecular determinants for SUMO-activating enzyme subcellular localization in plants

2020 ◽  
Author(s):  
Abraham Más ◽  
Laura Castaño-Miquel ◽  
Lorenzo Carretero-Paulet ◽  
Núria Colomé ◽  
Francesc Canals ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Regulatory Mechanism ◽  
Large Subunit ◽  
Post Translational Modification ◽  
Nuclear Localization Signals ◽  
Sumo Conjugation ◽  
Phylogenetic Studies ◽  
Molecular Determinants ◽  
Evolutionary Role

AbstractPost-translational modification by Small Ubiquitin-related Modifier (SUMO) is an essential regulatory mechanism in eukaryotes. In the cell, SUMO conjugates are highly enriched in the nucleus and, consistently, SUMOylation machinery components are mainly nuclear. Nonetheless, cytosolic SUMO targets also exist and the mechanisms that facilitate SUMO conjugation in the cytosol are unknown. Here, we show that the nuclear localization of the Arabidopsis SUMO activating enzyme large subunit SAE2 is dependent on two nuclear localization signals, the canonical NLS1 and the non-canonical NLS2 identified and validated here. NLS2 is proteolytic processed from SAE2 during seed development, facilitating SAE2 enrichment in the cytosol. Results obtained using transgenic plants expressing different SAE2 proteoforms suggest that SAE2 cytosolic enrichment could constitute a rapid signal for growth arrest. Phylogenetic studies indicated that the Arabidopsis NLS1-NLS2 structural organization is conserved only in seed plants, providing a potential evolutionary role of cytosolic SUMOylation in seed appearance.

scholarly journals Protein Acetylation Induced by Dichloroacetate (DCA) Treatment is Associated with Decreased Respiration in Cultured Hepatocytes: Preliminary Results

2019 ◽  
Author(s):  
Jesse G. Meyer
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Physiological Role ◽  
Pyruvate Dehydrogenase Kinase ◽  
Protein Acetylation ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Excess Production ◽  
Lysine Residues ◽  
Genetic Perturbations

AbstractProtein post-translational modification (PTM) by acetylation at the ε-amine on lysine residues in proteins regulates various cellular processes including transcription and metabolism. Several metabolic and genetic perturbations are known to increase acetylation of various proteins. Hyper-acetylation can also be induced using deacetylase inhibitors. While there is much interest in discovering drugs that can reverse protein acetylation, pharmacological tools that increase non-enzymatic protein acetylation are needed in order to understand the physiological role of excess protein acetylation. In this study, I assessed whether inhibition of pyruvate dehydrogenase kinase (PDHK) could cause protein hyper-acetylation due to excess production of acetyl-CoA by pyruvate dehydrogenase (PDH). Western blot of total protein from dichloroacetate (DCA) treated hepatocytes with anti-acetyl-lysine antibody showed increased protein acetylation, and seahorse respirometry of DCA pretreated hepatocytes indicated a subtle decrease in basal and maximal respiratory capacity.

scholarly journals Acetylproteomics analyses reveal critical features of lysine-ε-acetylation in Arabidopsis and a role of 14-3-3 protein acetylation in alkaline response

2022 ◽  
Vol 2 (1) ◽  
Author(s):  
Jianfei Guo ◽  
Xiaoqiang Chai ◽  
Yuchao Mei ◽  
Jiamu Du ◽  
Haining Du ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Alkaline Stress ◽  
Lysine Acetylation ◽  
Protein Acetylation ◽  
Post Translational Modification ◽  
Evolutionarily Conserved ◽  
Lysine Residues ◽  
Protein Lysine Acetylation ◽  
Subsequent Activation

AbstractLysine-ε-acetylation (Kac) is a post-translational modification (PTM) that is critical for metabolic regulation and cell signaling in mammals. However, its prevalence and importance in plants remain to be determined. Employing high-resolution tandem mass spectrometry, we analyzed protein lysine acetylation in five representative Arabidopsis organs with 2 ~ 3 biological replicates per organ. A total of 2887 Kac proteins and 5929 Kac sites were identified. This comprehensive catalog allows us to analyze proteome-wide features of lysine acetylation. We found that Kac proteins tend to be more uniformly expressed in different organs, and the acetylation status exhibits little correlation with the gene expression level, indicating that acetylation is unlikely caused by stochastic processes. Kac preferentially targets evolutionarily conserved proteins and lysine residues, but only a small percentage of Kac proteins are orthologous between rat and Arabidopsis. A large portion of Kac proteins overlap with proteins modified by other PTMs including ubiquitination, SUMOylation and phosphorylation. Although acetylation, ubiquitination and SUMOylation all modify lysine residues, our analyses show that they rarely target the same sites. In addition, we found that “reader” proteins for acetylation and phosphorylation, i.e., bromodomain-containing proteins and GRF (General Regulatory Factor)/14-3-3 proteins, are intensively modified by the two PTMs, suggesting that they are main crosstalk nodes between acetylation and phosphorylation signaling. Analyses of GRF6/14-3-3λ reveal that the Kac level of GRF6 is decreased under alkaline stress, suggesting that acetylation represses plant alkaline response. Indeed, K56ac of GRF6 inhibits its binding to and subsequent activation of the plasma membrane H+-ATPase AHA2, leading to hypersensitivity to alkaline stress. These results provide valuable resources for protein acetylation studies in plants and reveal that protein acetylation suppresses phosphorylation output by acetylating GRF/14-3-3 proteins.

scholarly journals Monoclonal anti-AMP-antibodies reveal broad and diverse AMPylation patterns in cancer cells

2020 ◽  
Author(s):  
Dorothea Höpfner ◽  
Joel Fauser ◽  
Marietta S. Kaspers ◽  
Christian Pett ◽  
Christian Hedberg ◽  
...  
Keyword(s):  
Amino Acid ◽  
Western Blot ◽  
Recent Progress ◽  
Regulatory Mechanism ◽  
Target Identification ◽  
Adenosine Monophosphate ◽  
Post Translational Modification ◽  
Highly Sensitive ◽  
Amino Acid Side Chains

AbstractAMPylation is a post-translational modification that modifies amino acid side chains with adenosine monophosphate (AMP). Recent progress in the field reveals an emerging role of AMPylation as a universal regulatory mechanism in infection and cellular homeostasis, however, generic tools to study AMPylation are required. Here, we describe three monoclonal anti-AMP antibodies (mAbs) from mouse which are capable of protein backbone independent recognition of AMPylation, in denatured (Western Blot) as well as native (ELISA, IP) applications, thereby outperforming previously reported tools. These antibodies are highly sensitive and specific for AMP modifications, highlighting their potential as tools for new target identification, as well as for validation of known targets. Interestingly, applying the anti-AMP mAbs to various cancer cell lines reveals a previously undescribed broad and diverse AMPylation pattern. In conclusion, the anti-AMP mABs will aid the advancement of understanding AMPylation and the spectrum of modified targets.

Pathogenesis of Age-related Cataract: a systematic review of proteomic studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Christina Karakosta ◽  
Argyrios Tzamalis ◽  
Michalis Aivaliotis ◽  
Ioannis Tsinopoulos
Keyword(s):  
Systematic Review ◽  
Oxidant Stress ◽  
Critical Role ◽  
Human Lens ◽  
Nuclear Cataract ◽  
Cataract Formation ◽  
Post Translational Modification ◽  
Ability To Act ◽  
Age Related

Background/Objective:: The aim of this systematic review is to identify all the available data on human lens proteomics with a critical role to age-related cataract formation in order to elucidate the physiopathology of the aging lens. Materials and Methods:: We searched on Medline and Cochrane databases. The search generated 328 manuscripts. We included nine original proteomic studies that investigated human cataractous lenses. Results:: Deamidation was the major age-related post-translational modification. There was a significant increase in the amount of αA-crystallin D-isoAsp58 present at all ages, while an increase in the extent of Trp oxidation was apparent in cataract lenses when compared to aged normal lenses. During aging, enzymes with oxidized cysteine at critical sites included GAPDH, glutathione synthase, aldehyde dehydrogenase, sorbitol dehydrogenase, and PARK7. Conclusion:: D-isoAsp in αA crystallin could be associated with the development of age-related cataract in human, by contributing to the denaturation of a crystallin, and decreasing its ability to act as a chaperone. Oxidation of Trp may be associated with nuclear cataract formation in human, while the role of oxidant stress in age-related cataract formation is dominant.

Music and Gesture

2017 ◽  
Author(s):  
Lawrence M. Zbikowski
Keyword(s):  
Dynamic Processes ◽  
Thought Processes ◽  
Human Communication ◽  
Charlie Chaplin ◽  
Swing Time ◽  
The Relationship

This chapter explores the relationship between music and physical gesture, drawing on recent research on the spontaneous gestures that accompany speech. Such gestures appear to be motivated by thought processes that are independent from speech and that in many cases offer analogs for dynamic processes. The chapter outlines the infrastructure for human communication that supports language and gesture as well as music. This outline provides a framework for exploring how music and gesture are similar and for how they are different. These comparisons are made through analyses of the movements Fred Astaire makes while accompanying himself at the piano in the 1936 film Swing Time and those Charlie Chaplin makes to Brahms’s Hungarian Dance No. 5 in the 1941 film The Great Dictator. These analyses further explicate the role of syntactic processes and syntactic layers in musical grammar and introduce referential frameworks, which serve as perceptual anchors for syntactic processes.

Situational Breakdowns

2019 ◽  
Author(s):  
Anne Nassauer
Keyword(s):  
United States ◽  
Large Scale ◽  
Contextual Factors ◽  
The United States ◽  
Social Outcomes ◽  
Dynamic Processes ◽  
Collective Decisions ◽  
Different Types ◽  
The Impact

This book provides an account of how and why routine interactions break down and how such situational breakdowns lead to protest violence and other types of surprising social outcomes. It takes a close-up look at the dynamic processes of how situations unfold and compares their role to that of motivations, strategies, and other contextual factors. The book discusses factors that can draw us into violent situations and describes how and why we make uncommon individual and collective decisions. Covering different types of surprise outcomes from protest marches and uprisings turning violent to robbers failing to rob a store at gunpoint, it shows how unfolding situations can override our motivations and strategies and how emotions and culture, as well as rational thinking, still play a part in these events. The first chapters study protest violence in Germany and the United States from 1960 until 2010, taking a detailed look at what happens between the start of a protest and the eruption of violence or its peaceful conclusion. They compare the impact of such dynamics to the role of police strategies and culture, protesters’ claims and violent motivations, the black bloc and agents provocateurs. The analysis shows how violence is triggered, what determines its intensity, and which measures can avoid its outbreak. The book explores whether we find similar situational patterns leading to surprising outcomes in other types of small- and large-scale events: uprisings turning violent, such as Ferguson in 2014 and Baltimore in 2015, and failed armed store robberies.

Musical shape and feeling

2017 ◽  
Author(s):  
Daniel Leech-Wilkinson
Keyword(s):  
Everyday Life ◽  
Recent Work ◽  
Sensory Perception ◽  
Dynamic Processes ◽  
Sensorimotor System ◽  
Musical Sound ◽  
Sensory Mode ◽  
Daniel Stern

The concept of shape is widely used by musicians in talking and thinking about performance, yet the mechanisms that afford links between music and shape are little understood. Work on the psychodynamics of everyday life by Daniel Stern and on embodiment by Mark Johnson suggests relationships between the multiple dynamics of musical sound and the dynamics of feeling and motion. Recent work on multisensory and precognitive sensory perception and on the role of bimodal neurons in the sensorimotor system helps to explain how shape, as a percept representing changing quantity in any sensory mode, may be invoked by dynamic processes at many stages of perception and cognition. These processes enable ‘shape’ to do flexible and useful work for musicians needing to describe the quality of musical phenomena that are fundamental to everyday musical practice and yet too complex to calculate during performance.

scholarly journals System-wide identification and prioritization of enzyme substrates by thermal analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amir Ata Saei ◽  
Christian M. Beusch ◽  
Pierre Sabatier ◽  
Juan Astorga Wells ◽  
Hassan Gharibi ◽  
...  
Keyword(s):  
Thermal Analysis ◽  
Thioredoxin Reductase ◽  
Structural Level ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Enzyme Substrate ◽  
Thioredoxin Reductase 1 ◽  
Enzyme Substrates ◽  
Substrate Proteins

AbstractDespite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.

scholarly journals Functions of Dendritic Cells and Its Association with Intestinal Diseases

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 583
Author(s):  
Ze-Jun Yang ◽  
Bo-Ya Wang ◽  
Tian-Tian Wang ◽  
Fei-Fei Wang ◽  
Yue-Xin Guo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Immune System ◽  
Regulatory Mechanism ◽  
Intestinal Tumors ◽  
Regulatory Relationship ◽  
Intestinal Diseases ◽  
Inflammatory Bowel ◽  
Plasmacytoid Dcs

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), serve as the sentinel cells of the immune system and are responsible for presenting antigen information. Moreover, the role of DCs derived from monocytes (moDCs) in the development of inflammation has been emphasized. Several studies have shown that the function of DCs can be influenced by gut microbes including gut bacteria and viruses. Abnormal changes/reactions in intestinal DCs are potentially associated with diseases such as inflammatory bowel disease (IBD) and intestinal tumors, allowing DCs to be a new target for the treatment of these diseases. In this review, we summarized the physiological functions of DCs in the intestinal micro-environment, their regulatory relationship with intestinal microorganisms and their regulatory mechanism in intestinal diseases.

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