Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MTORC1 dependent lipid signalling drives acute proteolytic rewiring of mitochondria by YME1L

ABSTRACT: mTORC1 dependent lipid signalling drives acute proteolytic rewiring of mitochondria by YME1L

PROVIDER: PRJNA552462 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR9640040_1.fastq.gz	Fastqsanger.gz
	SRR9640040_2.fastq.gz	Fastqsanger.gz
	SRR9640041_1.fastq.gz	Fastqsanger.gz
	SRR9640041_2.fastq.gz	Fastqsanger.gz
	SRR9640042_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

mTORC1 dependent lipid signalling drives acute proteolytic rewiring of mitochondria by YME1L

Project description:Metabolic reprogramming of mitochondria occurs during development, cell differentiation and in disease and is coupled to changes in mitochondrial mass and shape. Here, we demonstrate that the i-AAA protease YME1L rewires the proteome of pre-existing mitochondria in response to hypoxia or nutrient starvation. Inhibition of mTORC1 induces a lipid signalling cascade via the phosphatidic acid phosphatase LIPIN1, which decreases phosphatidylethanolamine levels in mitochondrial membranes and promotes proteolysis. YME1L degrades mitochondrial protein translocases, lipid transfer proteins and metabolic enzymes to acutely limit mitochondrial biogenesis and support cell growth. YME1L-mediated mitochondrial reshaping ensures spheroid and xenograft growth of pancreatic ductal adenocarcinoma (PDAC) cells. Similar mitochondrial proteome changes occur in tumour tissues of PDAC patients, suggesting that YME1L is relevant to the pathophysiology of specific solid tumours. Our results identify the mTORC1-LIPIN1-YME1L axis as a novel post-translational regulator of mitochondrial proteostasis at the interface of metabolism and mitochondrial dynamics.

2019-08-28 | GSE133753 | GEO

YME1L1 KO Hypoxia Proteome - Lipid signalling drives proteolytic rewiring of mitochondria by YME1L

Project description:Mitochondria are central metabolic hubs whose structure and function dynamically adapt to changing metabolic demands and environmental challenges. Metabolic reprogramming of mitochondria occurs during development, cell differentiation and in disease and is coupled to changes in mitochondrial mass and shape. Here, we demonstrate that the i-AAA protease YME1L rewires the proteome of pre-existing mitochondria in response to hypoxia or nutrient starvation. Inhibition of mTORC1 induces a lipid signalling cascade via the phosphatidic acid phosphatase LIPIN1, which decreases phosphatidylethanolamine levels in mitochondrial membranes and promotes proteolysis. YME1L degrades mitochondrial protein translocases, lipid transfer proteins and metabolic enzymes to acutely limit mitochondrial biogenesis and support cell growth. Similar mitochondrial proteome changes in tumor tissues of pancreatic ductal adenocarcinoma patients suggest that YME1L is relevant to the pathophysiology of hypoxic solid tumors. Our results identify the mTORC1-LIPIN1-YME1L axis as a novel post-translational regulator of mitochondrial proteostasis at the interface of metabolism and mitochondrial dynamics.

2019-08-21 | PXD011750 | Pride

KDM6A(UTX) is an epigenetic gatekeeper of mTORC1 signalling in cancer

Project description:KDM6A(UTX) is an epigenetic gatekeeper of mTORC1 signalling in cancer

| PRJNA650533 | ENA

Therapeutic interference with mTorc1 restricts inflammation-associated and Stat3-dependent gastro-intestinal tumourigenesis in mice

Project description:Gp130 receptor engagement on neoplastic cells provides a link by which an inflammatory microenvironment facilitates tumour promotion. Although hyperactivation of the gp130-dependent Stat3 signalling node is commonly observed in solid tumours, Stat3 remains a challenging therapeutic target. To mimic excessive Stat3 signalling, we molecularly validate the gp130FF mouse as a preclinical model for inflammation-associated intestinal-type gastric cancer (IGC), with aberrant mammalian target of rapamycin (mTOR) pathway activity as shared feature. Accordingly, administration of the mTorc1 inhibitor RAD001 reversibly reduced IGC burden in gp130FF mice and suppressed colitis-associated cancer in wild-type mice. Since the therapeutic effect of RAD001 occurs independently of Stat3 hyperactivation, which is also dispensable for gp130-dependent engagement of the PI3K/Akt/mTorc1 pathway, we conclude that mTorc1 signalling limits tumour promoting Stat3 activity The mouse whole-genome gene expression profiling was performed on Illumina's MouseWG-6 v2.0 Expression BeadChips for 24 mice, with 8 mice in each group (gp130WT antral tissue, gp130FF unaffected antral tissue and gp130FF tumour tissue).

2013-01-29 | E-GEOD-35808 | biostudies-arrayexpress

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor and estrogen receptor signalling pathways in endocrine resistant breast cancer

Project description:Our data supports the potential combination of inhibition of ERBB2/3 signalling with mTORC1 perturbation and endocrine therapy in patients who have relapsed on endocrine therapy and retain a functional ER.

2018-08-01 | GSE112401 | GEO

KDM6A(UTX) is an epigenetic gatekeeper of mTORC1 signalling in cancer

Project description:Large-scale genome sequencing efforts of human tumors identified epigenetic modifiers as one of the most frequently mutated gene class in human cancer. However, how these mutations drive tumor development and progression is largely unknown. Here, we identify the histone demethylase KDM6A as an important tumor suppressor in solid cancers, such as liver cancer and pancreatic cancer. KDM6A-deficient tumors show hyperactivation of mTORC1 signaling, whereas endogenous KDM6A re-expression in established KDM6A-deficient tumors diminishes mTORC1 activity by fostering the expression of crucial negative pathway regulators, such as DEPTOR, TSC1, and TSC2, resulting in tumor regression. Importantly, KDM6A expression in human tumors correlates with mTORC1 activity and KDM6A-deficient tumors exhibit increased sensitivity to mTORC1 inhibition. Hence, our results link KDM6A-dependent epigenetic remodeling to mTORC1 signaling and provide a potential therapeutic strategy for KDM6A-deficient tumors.

2022-07-20 | GSE155630 | GEO

Expression data from MOLM-14 human acute myeloid leukemia cell line after mTORC1 inhibition by rapamycin

Project description:The objective of the sudy is to evalute the role of mTORC1 signalling in the regulation of the metabolism of MOLM-14 cells. We used microarrays to investigate gene expression in MOLM-14 cells after down-regulation of mTORC1 signalling by rapamycin.

2017-08-14 | GSE95172 | GEO

mTORC1 Activation is not sufficient to suppress hepatic PPAR-a signalling or ketogenesis

Project description:mTORC1 Activation is not sufficient to suppress hepatic PPAR-a signalling or ketogenesis

| PRJNA695502 | ENA

TSC-Insensitive Rheb Mutations Induce Oncogenic Transformation Through a Combination of Hyperactive mTORC1 Signalling and Metabolic Reprogramming

Project description:The mechanistic target of rapamycin complex 1 (mTORC1) is an important regulator of cellular metabolism that is commonly hyperactivated in cancer. Recent cancer genome screens have identified multiple mutations in Ras-homolog enriched in brain (Rheb), the primary activator of mTORC1, that might act as driver oncogenes through aberrant hyperactivation of mTORC1. Here, we show that a number of recurrently occurring Rheb mutants drive hyperactive mTORC1 signalling through differing levels of insensitivity to the primary inactivator of Rheb, Tuberous Sclerosis Complex. We show that two activated mutants, Rheb-T23M and E40K, strongly drive increased cell growth and proliferation and anchorage-independent growth resulting in enhanced tumour growth in vivo. Proteomic analysis of cells expressing the mutations revealed, surprisingly, that these two mutants promote distinct oncogenic pathways with Rheb-T23M driving metabolic reprogramming and an increased reliance of glycolysis, while Rheb-E40K interacts with AMPK to regulate eukaryotic elongation factor 2 (eEF2) and autophagy. Our findings suggest that unique ‘bespoke’ combination therapies may be utilised to treat cancers according to which Rheb mutant they harbour.

2021-04-22 | PXD017006 | Pride

Therapeutic interference with mTorc1 restricts inflammation-associated and Stat3-dependent gastro-intestinal tumourigenesis in mice

2013-01-29 | GSE35808 | GEO