Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mitochondrial-Derived Compartments Facilitate Cellular Adaptation to Amino Acid Stress

ABSTRACT: Amino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, the mitochondrial-derived compartment (MDC), functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and deplete SLC25A nutrient carriers and their associated import receptor Tom70 from the organelle. Generation of MDCs promotes amino acid catabolism, and their formation occurs simultaneously with transporter removal at the plasma membrane via the multi-vesicular body (MVB) pathway. Combined loss of vacuolar amino acid storage, MVBs and MDCs renders cells sensitive to high amino acid stress. Thus, we propose that MDCs operate as part of a coordinated cell network that facilitates amino acid homoeostasis through post-translational nutrient transporter remodeling.

ORGANISM(S): Yeast Saccharomyces Cerevisiae

TISSUE(S): Yeast Cells

SUBMITTER: Adam Hughes

PROVIDER: ST001901 | MetabolomicsWorkbench | Thu Jul 22 00:00:00 BST 2021

REPOSITORIES: MetabolomicsWorkbench

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	mwtab	Other

Items per page:

1 - 1 of 1

Similar Datasets

Exonuclease Xrn1 regulates TORC1 signaling in response to SAM availability

Project description:Autophagy is a conserved process of cellular self-digestion that promotes survival during nutrient stress. In yeast, methionine starvation is sufficient to induce autophagy. One pathway of autophagy induction is governed by the SEACIT complex, which regulates TORC1 activity in response to amino acids through the Rag GTPases Gtr1 and Gtr2 This work identifies an unexpected yet critical role for Xrn1 in nutrient sensing and growth control that extends beyond its canonical housekeeping function in RNA degradation and indicates an avenue for RNA metabolism to function in amino acid signaling into TORC1.

2023-10-19 | GSE226779 | GEO

Amino acid supplementation for enhancing recombinant protein production in E. coli

Project description:Amino acid starvation during recombinant protein production (RPP) induces metabolic stress to cellular host which results in reduced productivity of the recombinant bioprocess. In present study, supplementation of amino acids in a chemically defined medium showed several folds increase in recombinant product titers in E. coli BL21 DE3 strain. To understand, the effect of amino acid supplementation in alleviating cellular stress during RPP a deep insight of cellular physiology must be studied. Here, we performed transcriptomic analysis of E. coli expressing a recombinant protein in two different conditions: with (5 mM of all 20 amino acids) as test and without supplementation of amino acids as control. RNA-seq data revealed downregulation of several genes associated with stress in test culture confirming the critical role of amino acids supplementation in improving RPP.

2020-05-18 | GSE138044 | GEO

Genetic deletion or pharmacologic blockade of the amino acid transporter Slc6a14 in mice suppresses breast cancer induced by Polyoma middle T oncogene

Project description:Tumor cells have an increased need for amino acids. Mammalian cells cannot synthesize essential amino acids; they must obtain these amino acids via specific transporters. Glutamine, though a non-essential amino acid, is critical for tumor cells (glutamine addiction). Entry of amino acids into tumor cells is enhanced by upregulation of specific transporters. If the transporters that are specifically induced in tumor cells are identified, blockade of the induced transporters would constitute a logical strategy for cancer treatment. The transporter SLC6A14 is unique and transports all essential amino acids as well as glutamine and is expressed only at low levels in normal tissues, but induced in colon cancer and in ER+ breast cancer. We have now established the potential of this transporter as a drug target for breast cancer treatment using genetic and pharmacologic approaches. We then examined the progression of breast cancer in Polyoma middle T antigen (Py-MT) Tg mouse on Slc6a14+/+ and Slc6a14-/- background using microarray analysis.

2015-08-05 | GSE56612 | GEO

Genetic deletion or pharmacologic blockade of the amino acid transporter Slc6a14 in mice suppresses breast cancer induced by Polyoma middle T oncogene

2015-08-05 | E-GEOD-56612 | biostudies-arrayexpress

Reduced sphingolipid biosynthesis modulates proteostasis networks to enhance longevity

Project description:Treating Saccharomyces cerevisiae cells with myriocin reduces the intracellular free pool of most amino acids. We find that transcriptional changes within the first 6 hours of drug treatment seem to have little impact on free pool changes. Rather the changes are driven early by post-translational events including impaired amino acid transporter activity, due to a reduced rate of sphingolipid biosynthesis, and an increased rate of endocytosis of at least some amino acid transporters, particularly the major methionine transporter Mup1.

2023-01-01 | GSE199904 | GEO

Expression profiling of B.subtils SMY wild-type, (p)ppGpp0, ΔcodY (p)ppGpp0 and guaB- (p)ppGpp0 cells upon amino acid starvation (RHX) or guanosine (Guo) treatment.

Project description:The nucleotide (p)ppGpp is crucial for viability during amino acid limitation in bacteria, yet how it accomplishes this remains unknown. We found that the absence of (p)ppGpp in Bacillus subtilis cells leads to multiple amino acid auxotrophy, and that (p)ppGpp allows for prototrophy by reducing GTP levels. We provide evidence that reduction of GTP levels relieves the requirements for branched-chain amino acids primarily by preventing hyperactivity of the GTP-dependent transcriptional regulator CodY, but that GTP levels can also play an important role in regulating transcription of many amino acid biosynthesis genes independently of CodY. Thus, CodY-dependent and independent regulation of transcription by GTP levels plays overlapping yet distinct physiological roles in allowing amino acid prototrophy. Finally, supplementing these required amino acids does not protect against cell death upon nutrient downshift, but allows for sustained growth following this transition. We conclude that regulation of GTP levels by (p)ppGpp allows cells to adapt to conditions of amino acid limitation by first allowing survival during shifting nutrient conditions, and then allowing amino acid prototrophy by transcriptionally regulating amino acid biosynthesis. This strategy may be used to ensure viability during amino acid limitation in evolutionarily divergent bacteria.

2013-11-01 | GSE41501 | GEO

Transcriptomes of enriched mouse islet alpha cells

Project description:Glucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids and compensatory glucagon hypersecretion involving expansion of pancreatic a cell mass. Recent findings indicate that hyperaminoacidemia triggers pancreatic a cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative a cells and that Slc38a5 controls the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased a cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. These results show that Slc38a5 is a key component of the feedback circuit between glucagon receptor signaling in the liver and amino-acid-dependent regulation of pancreatic a cell mass in mice.

2017-06-21 | GSE90116 | GEO

Expression profiling of B.subtils SMY wild-type, (p)ppGpp0, M-NM-^TcodY (p)ppGpp0 and guaB- (p)ppGpp0 cells upon amino acid starvation (RHX) or guanosine (Guo) treatment.

2013-11-01 | E-GEOD-41501 | biostudies-arrayexpress

Differential yeast gene transcription during brewery propagation

Project description:The aim of this study was to determine the transcriptomic response of Saccharomyces pastorianus to environmental change during brewery propagation. Utilization of amino acids and fermentable carbohydrates during full-scale brewery propagation was compared to the simultaneous changes occurring in the yeast transcriptome. Transcription profiles were observed to fall within one of four different groups and the greatest changes were observed to occur within the first eight hours following inoculation. Nutrient uptake was at its greatest during this period and many genes involved in the utilization of amino acids and carbohydrates were activated. There was also a significant derepression response following monosaccharide exhaustion. A number of stress response genes were activated following inoculation, indicating a possible osmotic stress response. Nutrient limitation did not appear to initiate a significant stress response, but did activate genes involved in pseudohyphal growth and meiosis, despite the fact that neither biological process occurs in the strain utilized. The first hours after inoculation into propagation wort are particularly active with respect to nutrient utilization and transcriptional change. It is likely that this period is particularly stressful for the yeast cells though there is no evidence of viability loss and it may be concluded that the yeast cell can cope with this level of stress, possibly aided by the dynamic response of the transcriptome. Keywords: amino acid, brewing, carbohydrate, microarray, propagation, transcription, yeast GeneChip analyses were performed to determine the transcriptomic response of Saccharomyces pastorianus to environmental change during brewery propagation. Triplicate samples were taken immediately after inoculation and at intervals 4h, 8h, and 30h.

2009-06-02 | E-GEOD-16376 | biostudies-arrayexpress

Transcriptomic analysis of Campylobacter jejuni grown in medium containing serine as a main energy source

Project description:Campylobacter jejuni is one of the most important causes of food-borne diseases in industrialized countries. It is known that amino acids are important nutrient source for this pathogen, because C. jejuni lacks enzymes related to glycolysis. However, the characteristics on metabolism of C. jejuni grown in the nutrient restricted medium with a specific amino acid is not fully elucidated. This study shows that C. jejuni NCTC11168 grew well in the nutrient restricted medium containing serine, aspartate, glutamate, and proline. The single subtraction of serine significantly reduced the growth, while three other amino acids did not, suggesting the priority of serine among the four amino acids. In the transcriptomic analysis of C. jejuni NCTC11168 grown in medium with serine as a main energy source. Serine seemed to be sensed by some chemoreceptors and the C. jejuni might reached an adaptation stage with active growth. That is, the expression of flagellar assembly components was downregulated and the biosynthesis of multiple amino acids and nucleotide sugars were upregulated. These data suggest the higher requirement of serine as a nutrient of C. jejuni NCTC11168.

2018-09-17 | GSE119472 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data