A Comprehensive Atlas of Protein Turnover Rates in Murine Tissues
Ontology highlight
ABSTRACT:
INSTRUMENT(S): QEHF Orbitrap
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Nathan Welham Lloyd Smith
PROVIDER: MSV000086426 | MassIVE | Sat Nov 07 19:25:00 GMT 2020
REPOSITORIES: MassIVE
Similar Datasets
Project description: Not available
| S-EPMC8626426 | biostudies-literature
Project description:Within a cell, proteins are in a dynamic state of turnover and are continuously synthesized and degraded. As an energetically expensive cellular process, protein turnover can have two opposing effects on maintaining a healthy proteome during the lifespan of an organism. Rapid protein turnover can replace old and damaged proteins with newly synthesized proteins. However, the high energetic demands of this process can potentially generate damaging reactive oxygen species that comprise the long-term health of the proteome. Thus, the relationship between aging, protein turnover kinetics and energetic demands of an organism remain unclear. Here, we used a proteomic approach to measure global rates of protein turnover within cultured fibroblasts isolated from a number of species with a wide range of lifespans. We show that organismal lifespan is negatively correlated with global rates of turnover. By further comparing cells from mice and naked mole rats (a short-lived and long-lived rodent species, respectively) we show that the latter has slower rates of turnover, lower levels of ATP production and reduced cellular ROS levels. Despite its slower rate of protein turnover, naked mole rat cells are able to tolerate protein misfolding stress more effectively than mouse cells. We suggest that in lieu of rapid constitutive protein turnover, long-lived species such as the naked mole rat have may have evolved more energetically efficient mechanisms for selective clearance of damaged proteins.
2020-05-07 | PXD018325 | Pride
Project description:We measured miRNA turnover rates in 8 mammalian cell types post transcription inhibitors ActinomycinD (ActD) or 5,6-Dichlorobenzimidazole 1-β-D-ribofuranoside (DRB) treatment with miRNA expression profiling, generating 218 expression profiles on 528 endogenous miRNAs.
2015-02-05 | GSE46877 | GEO
Project description:Cellular protein abundance results from the relative rates of protein synthesis and protein degradation. Through combining in vivo stable isotope labelling and in-depth quantitative proteomics, we created a protein turnover atlas of wheat grain proteins during grain development. Our data demonstrate that protein turnover rates for 1447 unique wheat grain protein groups have an apparent spatiotemporal pattern that aids explanation of the 60% of variation in protein abundances that are not attributable to gene expression. Protein synthesis rates of individual proteins vary over 100 fold and degradation rates over 20 fold. Storage proteins have both higher synthesis and degradation rates than the overarching average rates of grain proteins in other functional categories, while those proteins involved in photosynthesis, DNA synthesis and glycolysis, by contrast, are house-keeping proteins that show low synthesis and degradation rates at all times. Approximately 20% of total grain ATP production through respiration is used for grain proteome biogenesis and maintenance, and the grain invests nearly half of this budget in storage protein synthesis alone. Degradation of storage proteins as a class of grain proteins also consumed a significant amount of the total ATP allocated to protein degradation processes. This analysis suggests that 20% of newly synthesized storage proteins are turned over rather than stored suggesting that this process is not energetically optimal. This approach to measure protein turnover rates at the proteome scale shows how different functional categories of grain proteins accumulate, calculates the costs of futile cycling of protein turnover during wheat grain development and identifies the most and the least stable wheat grain proteins.
2021-12-21 | PXD022231 | Pride
Project description:We have used dietary administration of stable isotope labelled lysine to assess protein turnover rates for proteins from four tissues in the bank vole, Myodes glareolus. The annotated genome for this species is not available, so protein identification was attained through cross-species matching to the mouse. For proteins for which confident identifications were derived, the pattern of lysine incorporation over 40d was used to define the rate of synthesis of individual proteins in the four tissues. The data were heavily filtered to retain a very high quality data-set of turnover rates for 1088 proteins. Comparative analysis of the four tissues revealed different median rates of degradation (kidney: 0.099 per day; liver 0.136 per day; heart, 0.054 per day and skeletal muscle, 0.035 per day). These data were compared with protein degradation rates from other studies on intact animals or from cells in culture.
2016-02-09 | PXD002054 | Pride
Project description:Oxygen deprivation and excess are both toxic to mammals. Thus, the body’s ability to adapt to varying oxygen tensions is critical for survival. While the transcriptional response to acute hypoxia has been well-studied, the post-translational effects of hypoxia and hyperoxia have been underexplored. In this study, we systematically investigate protein turnover rates in mouse heart, lung, and brain under different inhaled oxygen tensions. We find that the lung proteome is the most responsive to changes in oxygen tension, likely due to the direct exposure of alveoli to inhaled oxygen. In particular, several extracellular matrix (ECM) proteins such as collagens and laminins, are stabilized in the lung under both hypoxia and hyperoxia, suggesting their post-translational regulation. Furthermore, we validate our previous finding that complex 1 of the electron transport chain (ETC) is destabilized in hyperoxia, explaining the exacerbation of associated disease models by hyperoxia and rescue by hypoxia. Moreover, we nominate MYBBP1A as a novel transcriptional regulator in hyperoxic lung, particularly in the context of rRNA homeostasis. Overall, our study highlights the importance of the effects of oxygen tensions on protein turnover rates and identifies novel tissue-specific mediators of oxygen-dependent responses.
2023-12-10 | GSE234123 | GEO
Project description:In spite of its central role in biology and disease, protein turnover is a largely understudied aspect of most proteomic studies due to the complexity of computational workflows that analyze in-vivo turnover rates. To address this need, we developed a new computational tool, TurnoveR, to accurately calculate protein turnover rates from mass spectrometric analysis of metabolic labeling experiments in Skyline, a free and open-source proteomics software platform. TurnoveR is a straightforward graphical interface that enables seamless integration of protein turnover analysis into a traditional proteomics workflow in Skyline, allowing users to take advantage of the advanced and flexible data visualization and curation features built into the software. The TurnoveR computational pipeline performs critical steps to determine protein turnover rates, including isotopologue demultiplexing, precursor-pool correction, statistical analysis, and generation of data reports and visualizations. This workflow is compatible with many mass spectrometric platforms and re-capitulates turnover rates and differential changes in turnover rates between treatment groups calculated in previous studies. We expect that the addition of TurnoveR to the widely used Skyline proteomics software will facilitate wider utilization of protein turnover analysis in highly relevant biological models, including aging, neurodegeneration, and skeletal muscle atrophy.
2022-02-22 | MSV000088893 | MassIVE
Project description:Direct measurement of nucleosome turnover dynamics by using co-translational incorporation of the methionine (Met) surrogate azidohomoalaine (Aha) into proteins and subsequent ligation of biotin to Aha-containing proteins through the [3+2] cycloaddition reaction between the azide group of Aha and an alkyne linked to biotin. To measure turnover rates, we treat cells briefly with Aha, couple biotin to nucleosomes containing newly incorporated histones, affinity purify with strepavidin, wash stringently to remove non-histone proteins and H2A/H2B dimers, and analyze the affinity-purified DNA using tiling microarrays. We call this strategy 'CATCH-IT' for Covalent Attachment of Tags to Capture Histones and Identify Turnover. Keywords: Chromatin affinity-purification on microarray All experiments were done using strepavidin pulldown DNA cohybridized with total input DNA to the same array. Two channels per array, Cy5 and Cy3, were used in each experiment.
2010-05-27 | E-GEOD-19788 | biostudies-arrayexpress
Project description:Obese and lean-type pig breeds show obvious differences in adipose deposition and muscle growth; however, the molecular mechanisms underlying this phenotypic variation remains unclear. Landrace (a leaner, Western breed), Rongchang (a fatty, Chinese breed) and Tibetan (a feral, indigenous Chinese breed that has not undergone artificial selection) pig breeds were used in this study. We collected eight diverse adipose tissues and two phenotypically distinct skeletal muscle tissues from three well-defined pig models with distinct fat rates, and studied mRNA expression differences among breeds, males and females, and tissues. These results highlight some possible candidate genes for porcine adipose deposition and muscle growth and provide some data on which to base further studies of the molecular basis of energy metabolism. The mRNA expression differences of eight diverse adipose tissues and two phenotypically distinct skeletal muscle tissues from three well-defined pig models with distinct fat rates are measured.
2012-05-15 | E-GEOD-30343 | biostudies-arrayexpress
Project description:Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near saturating levels throughout the neuronal genome by mid-adolescence. Despite such accumulation, H3.3 containing nucleosomes remain highly dynamic–in a modification independent manner–to control neuronal- and glial- specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical, and previously undocumented, regulator of cell-type specific transcription and plasticity in mammalian brain. All RNA-seq samples were generated to test the impact of neuronal activity/adult physiological plasticity on histone turnover turnover mediated alterations in mRNA expression in the central nervous system. This was tested in cultured neurons and astrocytes, and embryonic/adult brain tissues
2015-06-23 | E-GEOD-69807 | biostudies-arrayexpress