Acetylation of the yeast Hsp40 chaperone protein Ydj1 regulates proteostasis and translational fidelity
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Eclipse
ORGANISM(S): Saccharomyces Cerevisiae (ncbitaxon:4932)
SUBMITTER: 
Andrew W Truman
PROVIDER: MSV000094536 | MassIVE | Sun Apr 14 18:08:00 BST 2024
SECONDARY ACCESSION(S): PXD051428
REPOSITORIES: MassIVE
Similar Datasets
Project description:We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine 635 was mutated to glutamine (K635Q). Male Acss1K635Q/K635Q mice were smaller with higher metabolic rate and blood acetate, and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1K635Q/K635Q mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis – consistent with nonalcoholic fatty liver disease (NAFLD). RNAseq analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD
2024-04-12 | GSE260582 | GEO
Project description:We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine 635 was mutated to glutamine (K635Q). Male Acss1K635Q/K635Q mice were smaller with higher metabolic rate and blood acetate, and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1K635Q/K635Q mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis – consistent with nonalcoholic fatty liver disease (NAFLD). RNAseq analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD.
2024-04-12 | GSE260581 | GEO
Project description:Purpose: The experiment aimed to elucidate possible global effects of Nup60 K467 acetylation on transcription in S.cerevisiae. Result: Neither acetyl-mimic nor deacetyl-mimic mutations in Nup60K467 cause major shifts in expression profile.
2022-06-16 | GSE199740 | GEO
Project description:N-terminal acetylation is one of the most common protein modifications in eukaryotes. The NatA complex is the dominant regulator of the N-acetylome in all eukaryotes. The Huntingtin yeast partner K (HYPK) physically interacts with the NatA/NAA50 comples in metazoan and we describe HYPK as a critical regulator of NatA acivity. This proteome dataset compares the HYPK mutation Arabidopsis lines hypk-1 and hypk-3 to wild type Arabidopsis.
2022-04-13 | PXD022120 | Pride
Project description:Enteric bacteria use up to 15% of their cellular energy for ammonium assimilation via glutamine synthetase (GS)/glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH), in response to low or high ammonium availability. However, the sensory mechanisms for effective and appropriate coordination between carbon metabolism and ammonium assimilation are not fully elucidated. Here, we report that, in Salmonella, carbon metabolism coordinates the activities of GS/GDH via functional reversible protein lysine acetylation. Glucose simultaneously promotes acetyltransferase Pat-mediated acetylation on Lys164 and Lys353 of GS to activate the adenylylated-GS by inducing its conformation change, while on Lys128 of GDH to inactivate the enzyme by impeding its catalytic center, respectively, which are reversed by deacetylase CobB-mediated deacetylation. Molecular dynamic (MD) simulations indicated that the acetylation activation of GS activity was adenylylation-dependent. Acetylation and deacetylation occur within minutes of ‘glucose shock’ to promptly adapt to ammonium/carbon variation and finely balance glutamine/glutamate synthesis. Acetylation can rehabilitate the growth tardiness of Salmonella mutant with chromosomal mimetic mutation of adenylylated-GS and thus help its survival in mice. Thus, glucose-driven acetylation integrates the signals of assimilation and carbon metabolism for proper growth control.
2023-06-21 | PXD039658 | Pride
Project description:A major challenge for metazoans is to ensure that different tissues, each expressing distinctive proteomes, are nevertheless well protected at an organismal level from proteotoxic stress. We show that expression of endogenous metastable proteins in muscle cells, which rely on chaperones for proper folding, induces a systemic stress response throughout multiple tissues of C. elegans. Suppression of misfolding in muscle cells can be achieved not only by enhanced expression of HSP90 in muscle cells but as effectively by elevated expression of HSP90 in intestine or neuronal cells. This cell-nonautonomous control of HSP90 expression relies upon transcriptional feedback between somatic tissues that is regulated by the FoxA transcription factor PHA-4. This transcellular chaperone signaling response maintains organismal proteostasis when challenged by a local tissue imbalance in folding and provides the basis for organismal stress-sensing surveillance.
| S-EPMC3955170 | biostudies-literature
Project description:Because a cell must adapt to different stresses and growth rates, its proteostasis system must too. How do cells detect and adjust proteome folding to different conditions? Here, we explore a biophysical cost-benefit principle, namely that the cell should keep its proteome as folded as possible at the minimum possible energy cost. This can be achieved by differential expression of chaperones-balancing foldases (which accelerate folding) against holdases (which act as parking spots). The model captures changes in the foldase-holdase ratio observed both within organisms during aging and across organisms of varying metabolic rates. This work describes a simple biophysical mechanism by which cellular proteostasis adapts to meet the needs of a changing growth environment.
| S-EPMC7769611 | biostudies-literature
Project description:Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discovered that neurons localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress. The most abundant dendritic chaperone mRNA encodes a constitutive heat shock protein 70 family member (HSPA8). Proteotoxic stress also enhanced HSPA8 mRNA translation efficiency in dendrites. Stress-mediated HSPA8 mRNA localization to the dendrites was impaired by depleting fused in sarcoma-an amyotrophic lateral sclerosis-related protein-in cultured mouse motor neurons and expressing a pathogenic variant of heterogenous nuclear ribonucleoprotein A2/B1 in neurons derived from human induced pluripotent stem cells. These results reveal a crucial and unexpected neuronal stress response in which RNA-binding proteins increase the dendritic localization of HSPA8 mRNA to maintain proteostasis and prevent neurodegeneration.
| S-EPMC10760236 | biostudies-literature
Project description:Chaperones are protein complexes that help to fold and disaggregate a cell's proteins. It is not understood how four major chaperone systems of Escherichia coli work together in proteostasis: the recognition, sorting, folding, and disaggregating of the cell's many different proteins. Here, we model this machine. We combine extensive data on chaperoning, folding, and aggregation rates with expression levels of proteins and chaperones measured at different growth rates. We find that the proteostasis machine recognizes and sorts a client protein based on two biophysical properties of the client's misfolded state (M state): its stability and its kinetic accessibility from its unfolded state (U state). The machine is energy-efficient (the sickest proteins use the most ATP-expensive chaperones), comprehensive (it can handle any type of protein), and economical (the chaperone concentrations are just high enough to keep the whole proteome folded and disaggregated but no higher). The cell needs higher chaperone levels in two situations: fast growth (when protein production rates are high) and very slow growth (to mitigate the effects of protein degradation). This type of model complements experimental knowledge by showing how the various chaperones work together to achieve the broad folding and disaggregation needs of the cell.
| S-EPMC5380058 | biostudies-literature
Project description:The transcription factor PLZF (promyelocytic leukemia zinc finger) is encoded by the BTB domain-containing 16 (Zbtb16) gene. Its repressor function regulates specific transcriptional programs. During the development of invariant natural killer T (NKT) cells, PLZF is expressed and directs their effector program but the detailed mechanisms underlying PLZF regulation of multi-stage NKT cell developmental program are not well understood. This study investigated the role of acetylation-induced PLZF activation on NKT cell development by analyzing mice expressing a mutant form of PLZF mimicking constitutive acetylation (PLZFON mice). NKT populations in PLZFON mice were reduced in proportion and numbers of cells, and the cells present were blocked at the transition from developmental stage 1 to stage 2. NKT cell subset differentiation was also altered, with T-bet+ NKT1 and RORt+ NKT17 subsets dramatically reduced, and the emergence of a T-bet-RORt- NKT cell subset with features of cells in early developmental stages rather than mature NKT2 cells. Preliminary analysis of DNA methylation patterns suggested that activated PLZF acts on the DNA methylation signature to regulate NKT cells’ entry into the early stages of development, while repressing maturation. In wild-type NKT cells, deacetylation of PLZF is possible, allowing subsequent NKT cell differentiation. Interestingly, development of other innate lymphoid and myeloid cells, that are dependent on PLZF for their generation, is not altered in PLZFON mice highlighting lineage specific regulation. Overall, we propose that specific epigenetic control of PLZF through acetylation levels is required to regulate normal NKT cell differentiation. Key points: Constitutive acetylation of PLZF (PLZFON) blocks NKT cell development. PLZFON might act on the DNA methylation signature to control gene expression. PLZF acetylation levels regulate normal NKT cell differentiation.
2021-05-24 | GSE128558 | GEO