scholarly journals Slowed Protein Turnover in Aging Drosophila Reflects a Shift in Cellular Priorities

2021 ◽  
Author(s):  
Evelyn S Vincow ◽  
Ruth E Thomas ◽  
Gennifer E Merrihew ◽  
Michael J MacCoss ◽  
Leo J Pallanck
Keyword(s):  
Quality Control ◽  
Protein Turnover ◽  
Protein Quality ◽  
Fruit Fly ◽  
Turnover Rates ◽  
High Turnover ◽  
Age Related ◽  
System Collapse ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Abstract The accumulation of protein aggregates and dysfunctional organelles as organisms age has led to the hypothesis that aging involves general breakdown of protein quality control. We tested this hypothesis using a proteomic and informatic approach in the fruit fly Drosophila melanogaster. Turnover of most proteins was markedly slower in old flies. However, ribosomal and proteasomal proteins maintained high turnover rates, suggesting that the observed slowdowns in protein turnover might not be due to a global failure of quality control. As protein turnover reflects the balance of protein synthesis and degradation, we investigated whether decreases in synthesis or decreases in degradation would best explain the observed slowdowns in protein turnover. We found that while many individual proteins in old flies showed slower turnover due to decreased degradation, an approximately equal number showed slower turnover due to decreased synthesis, and enrichment analyses revealed that translation machinery itself was less abundant. Mitochondrial complex I subunits and glycolytic enzymes were decreased in abundance as well, and proteins involved in glutamine-dependent anaplerosis were increased, suggesting that old flies modify energy production to limit oxidative damage. Together, our findings suggest that age-related proteostasis changes in Drosophila represent a coordinated adaptation rather than a system collapse.

scholarly journals Proteome dynamics during homeostatic scaling in cultured neurons

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Aline Ricarda Dörrbaum ◽  
Beatriz Alvarez-Castelao ◽  
Belquis Nassim-Assir ◽  
Julian D Langer ◽  
Erin M Schuman
Keyword(s):  
Protein Synthesis ◽  
Protein Function ◽  
Protein Turnover ◽  
Experimental Approach ◽  
Large Fraction ◽  
Synaptic Proteins ◽  
Turnover Rates ◽  
Cellular Environment ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Protein turnover, the net result of protein synthesis and degradation, enables cells to remodel their proteomes in response to internal and external cues. Previously, we analyzed protein turnover rates in cultured brain cells under basal neuronal activity and found that protein turnover is influenced by subcellular localization, protein function, complex association, cell type of origin, and by the cellular environment (Dörrbaum et al., 2018). Here, we advanced our experimental approach to quantify changes in protein synthesis and degradation, as well as the resulting changes in protein turnover or abundance in rat primary hippocampal cultures during homeostatic scaling. Our data demonstrate that a large fraction of the neuronal proteome shows changes in protein synthesis and/or degradation during homeostatic up- and down-scaling. More than half of the quantified synaptic proteins were regulated, including pre- as well as postsynaptic proteins with diverse molecular functions.

scholarly journals Protein turnover is elevated in muscle of mdx mice in vivo

1990 ◽  
Vol 268 (3) ◽  
pp. 795-797 ◽  
Author(s):  
P A MacLennan ◽  
R H T Edwards
Keyword(s):  
Protein Turnover ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mdx Mice ◽  
Turnover Rates ◽  
Wild Type ◽  
Dystrophin Deficiency ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

mdx mice lack the protein dystrophin, the absence of which causes Duchenne muscular dystrophy in humans. To examine how mdx mice maintain muscle mass despite dystrophin deficiency, we measured protein turnover rates in muscles of mdx and wild-type (C57BL/10) mice in vivo. At all ages studied, rates of muscle protein synthesis and degradation were higher in mdx than in C57BL/10 mice.

scholarly journals Spatial protein quality control and the evolution of lineage-specific ageing

2011 ◽  
Vol 366 (1561) ◽  
pp. 71-75 ◽  
Author(s):  
Thomas Nyström
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Division Of Labour ◽  
Cell Renewal ◽  
Periodic Cell ◽  
Age Related ◽  
Selective Forces ◽  
Rate Of Ageing ◽  
Protein Folding Disorders

Propagation of a species requires periodic cell renewal to avoid clonal extinction. Sexual reproduction and the separation of germ cells from the soma provide a mechanism for such renewal, but are accompanied by an apparently mandatory ageing of the soma. Data obtained during the last decade suggest that a division of labour exists also between cells of vegetatively reproducing unicellular organisms, leading to the establishment of a soma-like and germ-like lineage with distinct fitness and longevity characteristics. This division of labour in both bacteria and yeast entails segregation of damaged and aggregated proteins such that the germ-like lineage is kept free of damage to the detriment of the soma-like lineage. In yeast, this spatial protein quality control (SQC) encompasses a CCT-chaperonin-dependent translocation and merging of cytotoxic protein aggregates. This process is regulated by Sir2, a protein deacetylase that modulates the rate of ageing in organisms ranging from yeast to worms and flies. Recent data also demonstrate that SQC is intimately integrated with the machinery establishing proper cell polarity and that this machinery is required for generating a soma-like and germ-like lineage in yeast. Deciphering the details of the SQC network may increase our understanding of the development of age-related protein folding disorders and shed light on the selective forces that paved the way for polarity and lineage-specific ageing to evolve.

scholarly journals Versatile proteome labelling in fruit flies with SILAF

2019 ◽  
Author(s):  
Florian A. Schober ◽  
Ilian Atanassov ◽  
David Moore ◽  
Anna Wedell ◽  
Christoph Freyer ◽  
...  
Keyword(s):  
Protein Turnover ◽  
Cell Biology ◽  
Metabolic Regulation ◽  
Developmental Stages ◽  
Fruit Fly ◽  
Phosphorylation Sites ◽  
Turnover Rates ◽  
Post Translational Modification ◽  
Stable Isotope Labelling ◽  
Rapid Generation

ABSTRACTDrosophila melanogaster has been a working horse of genetics and cell biology for more than a century. However, proteomic-based methods have been limited due to technical obstacles, especially the lack of reliable labelling methods. Here, we advanced a chemically defined food source into stable-isotope labelling of amino acids in flies (SILAF). It allows for the rapid generation of a large number of flies with full incorporation of lysine-6. SILAF followed by fractionation and enrichment gave proteomic insights at a depth of 5,966 proteins and 7,496 phosphorylation sites, which substantiated metabolic regulation on enzymatic level. Furthermore, the label can be traced and predicts protein turnover rates during different developmental stages. The ease and versatility of the method actuates the fruit fly as an appealing model in proteomic and post-translational modification studies and it enlarges potential metabolic applications based on heavy amino acid diets.

scholarly journals Morpho-Biochemical and Protein Turnover Readings of Growing Geese Consuming Vitamin Supplements

2021 ◽  
Author(s):  
Evgenii Alevtinovich Grishin
Keyword(s):  
Protein Turnover ◽  
Oxygen Supply ◽  
Feed Additive ◽  
Aerobic Respiration ◽  
Vitamin Supplements ◽  
Turnover Rates ◽  
Metabolic Processes ◽  
High Turnover ◽  
Control Banding ◽  
Experimental Group

The aim of the study was to examine the protein turnover and morpho-biochemical readings of growing geese taking “Vitammin” feed additive. The control banding poultry received basic diet, the 1st experimental group received the diet with the addition of “Vitammin” in a dose of 0.2 ml/l of water, the 2nd experimental group – 0.5 ml/l of water. The research conducted showed that the use of “Vitammin” feed additive contributed to high-turnover rates and, consequently, improved the oxygen supply to organs and tissues in contrast to the control banding. In case of increasing the dose the additive it was noted that the rates of aerobic respiration increased as well, which is typical for the augmentation of metabolic processes and, subsequently, productivity.

scholarly journals Quantitative Temporal Analysis of Protein Dynamics in Maladaptive Cardiac Remodeling

2018 ◽  
Author(s):  
Daniel B. McClatchy ◽  
Yuanhui Ma ◽  
David A. Liem ◽  
Dominic C.M. Ng ◽  
Peipei Ping ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Protein Turnover ◽  
Heart Diseases ◽  
Temporal Analysis ◽  
Complex Nature ◽  
The Novel ◽  
Turnover Rates ◽  
Biochemical Mechanisms ◽  
And Oxidative Stress ◽  
Synthesis And Degradation

AbstractMaladaptive cardiac remodeling (MCR) is a complex dynamic process common to many heart diseases. MCR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of MCR, but greater insight into the processes and mechanisms has the potential to identify new therapeutic targets. To provide a deeper understanding of this important cardiac process, we applied a new proteomic technique, PALM (Pulse Azidohomoalanine in Mammals), to quantitate the newly-synthesized protein (NSP) changes during the progression of isoproterenol (ISO)-induced MCR in the mouse left ventricle. This analysis revealed a complex combination of adaptive and maladaptive alterations at acute and prolonged time points including the identification of proteins not previously associated with MCR. We also combined the PALM dataset with our published protein turnover rate dataset to identify putative biochemical mechanisms underlying MCR. The novel integration of analyzing NSPs together with their protein turnover rates demonstrated that alterations in specific biological pathways (e.g., inflammation and oxidative stress) are produced by differential regulation of protein synthesis and degradation.

scholarly journals Serum extracellular vesicle miR-203a-3p content is associated with skeletal muscle mass and protein turnover during disuse atrophy and regrowth

2020 ◽  
Vol 319 (2) ◽  
pp. C419-C431
Author(s):  
Douglas W. Van Pelt ◽  
Ivan J. Vechetti ◽  
Marcus M. Lawrence ◽  
Kathryn L. Van Pelt ◽  
Parth Patel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Weight Bearing ◽  
Mirna Content ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Small noncoding microRNAs (miRNAs) are important regulators of skeletal muscle size, and circulating miRNAs within extracellular vesicles (EVs) may contribute to atrophy and its associated systemic effects. The purpose of this study was to understand how muscle atrophy and regrowth alter in vivo serum EV miRNA content. We also associated changes in serum EV miRNA with protein synthesis, protein degradation, and miRNA within muscle, kidney, and liver. We subjected adult (10 mo) F344/BN rats to three conditions: weight bearing (WB), hindlimb suspension (HS) for 7 days to induce muscle atrophy, and HS for 7 days followed by 7 days of reloading (HSR). Microarray analysis of EV miRNA content showed that the overall changes in serum EV miRNA were predicted to target major anabolic, catabolic, and mechanosensitive pathways. MiR-203a-3p was the only miRNA demonstrating substantial differences in HS EVs compared with WB. There was a limited association of EV miRNA content to the corresponding miRNA content within the muscle, kidney, or liver. Stepwise linear regression demonstrated that EV miR-203a-3p was correlated with muscle mass and muscle protein synthesis and degradation across all conditions. Finally, EV miR-203a-3p expression was significantly decreased in human subjects who underwent unilateral lower limb suspension (ULLS) to induce muscle atrophy. Altogether, we show that serum EV miR-203a-3p expression is related to skeletal muscle protein turnover and atrophy. We suggest that serum EV miR-203a-3p content may be a useful biomarker and future work should investigate whether serum EV miR-203a-3p content is mechanistically linked to protein synthesis and degradation.

Skeletal and cardiac muscle protein turnover during short-term cold exposure and rewarming in young rats

1996 ◽  
Vol 270 (6) ◽  
pp. R1231-R1239 ◽  
Author(s):  
S. E. Samuels ◽  
J. R. Thompson ◽  
R. J. Christopherson
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Cardiac Muscle ◽  
Cold Exposure ◽  
Growth Rates ◽  
Protein Turnover ◽  
Short Term ◽  
Ad Libitum ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Young animals exposed to cold environmental temperatures typically have decreased skeletal muscle accretion but increased heart masses. To explore these phenomena, we measured protein synthesis and degradation in vivo in cardiac and skeletal muscle in weanling rats during short-term cold exposure and rewarming. Control rats were housed at 25 degrees C throughout the experiment. Ad libitum-fed and pair-fed (to the intake of controls) rats were housed at 5 degrees C (cold) for 5 days and then at 25 degrees C (rewarmed) for another 5 days. Cold exposure decreased rates of protein accretion and synthesis in skeletal muscle, whereas degradation did not differ. The effects of cold exposure on skeletal muscle were similar in both pair-fed and ad libitum-fed rats, except growth was lower in pair-fed rats. In cardiac muscle, cold exposure increased rates of protein synthesis and degradation and resulted in increased cardiac mass. Results in pair-fed animals generally fell between those of control and ad libitum-fed cold rats. During rewarming, growth rates were not higher in skeletal muscle in ad libitum-fed re-warmed rats, although protein turnover returned toward control values; in pair-fed rats, it remained lower. In heart, growth rates of ad libitum-fed and pair-fed rewarmed rats decreased due to lower protein synthesis rates. These alterations appear to be consistent with a strategy designed to improve survival in cold environments.

scholarly journals Regulation of Ca2+-dependent protein turnover in skeletal muscle by thyroxine

1986 ◽  
Vol 240 (1) ◽  
pp. 269-272 ◽  
Author(s):  
R J Zeman ◽  
P L Bernstein ◽  
R Ludemann ◽  
J D Etlinger
Keyword(s):  
Skeletal Muscle ◽  
Protein Turnover ◽  
Proteinase Inhibitor ◽  
Thyroid Status ◽  
Protein Balance ◽  
Lysosomotropic Agent ◽  
Lysosomal Proteolysis ◽  
Dependent Protein ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Dantrolene, an agent that inhibits Ca2+ mobilization, improved protein balance in skeletal muscle, as thyroid status was increased, by altering rates of protein synthesis and degradation. Thyroxine (T4) caused increases in protein degradation that were blocked by leupeptin, a proteinase inhibitor previously shown to inhibit Ca2+-dependent non-lysosomal proteolysis in these muscles. In addition, T4 abolished sensitivity to the lysosomotropic agent methylamine and the autophagy inhibitor 3-methyladenine, suggesting that T4 inhibits autophagic/lysosomal proteolysis.

Effects of chronic sublethal ammonia and a simulated summer global warming scenario: protein synthesis in juvenile rainbow trout (Oncorhynchus mykiss)

1998 ◽  
Vol 55 (6) ◽  
pp. 1534-1544 ◽  
Author(s):  
Scott D Reid ◽  
T K Linton ◽  
J J Dockray ◽  
D G McDonald ◽  
C M Wood
Keyword(s):  
Protein Synthesis ◽  
Global Warming ◽  
Rainbow Trout ◽  
Oncorhynchus Mykiss ◽  
Protein Turnover ◽  
Warming Scenario ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Global Warming Scenario ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Protein synthesis, net accretion, and degradation in liver, gill, and white muscle and ribosomal translational efficiency and protein synthesis capacity in liver and gill were measured using a flooding dose of [3H]phenylalanine in juvenile rainbow trout (Oncorhynchus mykiss). The fish were chronically exposed (90 days) in hardwater to the presence or absence of sublethal ammonia (70 µmol total ammonia ·L-1) alone or in combination with a 2°C elevation in the normal temperature profile over the months of June-September 1993 (ambient temperature range 13-22°C). Chronic sublethal exposure to ammonia had little impact on gill protein synthesis and degradation (protein turnover) and even less in muscle. However, in the liver, both protein synthesis and degradation were stimulated following 60 days of the sublethal ammonia exposure. The 2°C elevation in temperature resulted in a slight increase in protein turnover in both gills and liver. However, during the period of peak water temperature, the 2°C elevation in temperature inhibited protein dynamics in these tissues. Overall, elevated environmental ammonia in combination with a summer global warming scenario would challenge the ability of fish to adapt to alterations in the quality of their environment, most notably during periods of peak temperatures.

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