Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

F1Fo-ATP synthase subunit determines lethal pathogenic fungi infection

ABSTRACT: Fungal infections, especially candidiasis and aspergillosis, claim an unacceptably high fatality rate. The energy ATP that is necessary for fungal cell growth and function is synthesized mainly through oxidative phosphorylation, with the key enzyme being F1Fo-ATP synthase. But it remains unknown how this enzyme affects fungal pathogenicity. Here, we show that F1Fo-ATP synthase δ subunit deletion abrogates lethal Candida albicans infection without affecting intracellular ATP concentrations or growth. Mechanistically, δ subunit deletion reduces Pfk1 activity by interrupting Pfk1 phosphorylation to trigger its conformation shifts, decreases downstream FBP level, blocks Ras1-dependent and -independent cAMP-PKA pathways, and curtails virulence factors. Based on these findings, we engineer a small molecule compound targeting δ subunit that effectively protects mice from succumbing to invasive candidiasis. In summary, our findings reveal that F1Fo-ATP synthase δ subunit determines lethal infection from pathogenic fungi and represents a potential therapeutic target.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic

SUBMITTER: æ°´ç§ æ

PROVIDER: MTBLS3332 | MetaboLights | 2021-10-08

REPOSITORIES: MetaboLights

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	MTBLS3332	Other
	FILES	Other
	a_MTBLS3332_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	files-all.json	Other
	i_Investigation.txt	Txt

Items per page:

1 - 5 of 7

Similar Datasets

F1Fo-ATP synthase subunit determines lethal infection in pathogenic fungi

Project description:Fungal infections, especially for candidiasis and aspergillosis, claim an unacceptably high fatality. However, the determining mechanism that promote fungal lethal infections are still elusive. The energy ATP necessary for fungal cell growth and function is synthesized mainly through oxidative phosphorylation, whose key enzyme is F1Fo-ATP synthase. Nonetheless, it remians unknown how this enzyme affects fungal pathogenicity. Here we show that F1Fo-ATP synthase subunit deletion completely abrogates C. albicans lethal infection rather than leading to remarkable intracellular ATP concentration and growth defect. Mechanically, subunit deletion reduces PFK1 activity via interrupting PFK1 phosphorylation to trigger its conformational change, decreases downstream FBP level, blocks Ras1-dependent and -independent cAMP-PKA pathway, and curtails virulence factors. Based on these findings, we engineer a small molecule compound aimed at subunit that effectively protects mice from succumbing to invasive candidiasis. In summary, our findings reveal that F1Fo-ATP synthase δ subunit determines the lethal infection of pathogenic fungi and represents a potential new therapeutic target.

2021-09-16 | PXD024729 | Pride

atpd_vs_WT

Project description:Series of 4 repetitions of hybridization of treatment (atpd) and control (WT) each. Comparison of Arabidopsis atpd mutant lacking ATP synthase delta subunit versus WT. D. Maiwald et al., Plant Physiol 133 (2003), pp. 191-202 Keywords: repeat sample

2004-12-31 | E-GEOD-1178 | biostudies-arrayexpress

atpd_vs_WT

2005-01-01 | GSE1178 | GEO

Acetate Fermentation facilitates survival of Mtb when respiration is inhibited

Project description:Respiratory ATP-synthesis is at present the only known mechanism for ATP synthesis in Mtb. This makes Mtb particularly vulnerable to inhibition of respiratory ATP synthase inhibitors such as TMC207, a novel compound for treatment of tuberculosis. We now provide first evidence that Mtb possesses a pathway that is fermentative in nature that could compensate lack of respiratory ATP synthesis. We identified acetate as a fermentation product in Mtb. Production of acetate was mediated by phosphotransacetylase (Pta) and acetate kinase (AckA). In acetate fermenting Mtb cultures, ATP levels remained stable despite inhibition of respiratory ATP synthase. Deletion of the PtaAckA pathway in Mtb decreased ATP content and impaired survival. This study provides evidence that in Mtb substrate level phosphorylation can compensate lack of oxidative phosphorylation, and thus facilitates survival of Mtb in the absence of respiration. Acetate fermentation contributes to adaptation to respiration-limiting conditions, and plays an important role in the emerging field of fermentative metabolism of Mtb.

2012-12-31 | GSE35484 | GEO

Acetate Fermentation facilitates survival of Mtb when respiration is inhibited

2012-12-31 | E-GEOD-35484 | biostudies-arrayexpress

Anticancer Agent Fb-Pmt Links The Thyroid Hormone Receptor On Integrin Αvβ3 To Cancer Cell Metabolism/Atp Generation [MOH-fbPMT]

Project description:Microarray analysis was carried out on human MOH cells exposed to fb-PMT (10e-6 M tetrac equivalent) for 24 h. fb-PMT significantly downregulated electron transport chain genes ATP5A1 (ATP synthase A1), ATP51, ATP5G2, COX6B1 (cytochrome c oxidase subunit 6B1), NDUFA8 (NADH dehydrogenase [ubiquinone] FA8), NDUFV2 and other NDUF genes, SLC25A6 (solute carrier group 2), UCP2 ([mitochondrial] uncoupling protein 2) and COX5A. The NDUF and ATP genes are also relevant to control of oxidative phosphorylation and transcription. Six additional NDUF genes linked to oxidative phosphorylation were affected. Conclusions. fb-PMT caused downregulation of expression of a panel of genes involved in electron transport, oxidative phosphorylation, and cytoplasmic ribosomal protein generation in MOH cells. A key component of the anticancer activity of fb-PMT relates to disordering of ATP generation mechanisms in tumor cells.

2022-07-01 | GSE180889 | GEO

ANTICANCER AGENT P-bi-TAT LINKS THE THYROID HORMONE RECEPTOR ON INTEGRIN αvβ3 TO CANCER CELL METABOLISM/ATP GENERATION II

Project description:Microarray analysis was carried out on human GBM cells exposed to P-bi-TAT (10-6 M tetrac equivalent) for 24 h. P-bi-TAT significantly downregulated electron transport chain genes ATP5A1 (ATP synthase A1), ATP51, ATP5G2, COX6B1 (cytochrome c oxidase subunit 6B1), NDUFA8 (NADH dehydrogenase [ubiquinone] FA8), NDUFV2 and other NDUF genes, SLC25A6 (solute carrier group 2), UCP2 ([mitochondrial] uncoupling protein 2) and COX5A. The NDUF and ATP genes are also relevant to control of oxidative phosphorylation and transcription. Six additional NDUF genes linked to oxidative phosphorylation were affected. Conclusions. P-bi-TAT caused downregulation of expression of a panel of genes involved in electron transport, oxidative phosphorylation, and cytoplasmic ribosomal protein generation in GBM cells. A key component of the anticancer activity of P-bi-TAT relates to disordering of ATP generation mechanisms in tumor cells.

2020-08-28 | GSE140449 | GEO

ANTICANCER AGENT P-bi-TAT LINKS THE THYROID HORMONE RECEPTOR ON INTEGRIN αvβ3 TO CANCER CELL METABOLISM/ATP GENERATION

2020-08-28 | GSE140272 | GEO

Anticancer Agent Fb-Pmt Links The Thyroid Hormone Receptor On Integrin Αvβ3 To Cancer Cell Metabolism/Atp Generation [Suit2-fbPMT]

Project description:Microarray analysis was carried out on human SUIT2 cells, cells exposed to fb-PMT (10-6 M tetrac equivalent) for 24 h. fb-PMT significantly downregulated electron transport chain genes ATP5A1 (ATP synthase A1), ATP51, ATP5G2, COX6B1 (cytochrome c oxidase subunit 6B1), NDUFA8 (NADH dehydrogenase [ubiquinone] FA8), NDUFV2 and other NDUF genes, SLC25A6 (solute carrier group 2), UCP2 ([mitochondrial] uncoupling protein 2) and COX5A. The NDUF and ATP genes are also relevant to control of oxidative phosphorylation and transcription. Six additional NDUF genes linked to oxidative phosphorylation were affected. Conclusions. fb-PMT caused downregulation of expression of a panel of genes involved in electron transport, oxidative phosphorylation, and cytoplasmic ribosomal protein generation in SUIT2 cells, cells. A key component of the anticancer activity of fb-PMT relates to disordering of ATP generation mechanisms in tumor cells.

2022-07-01 | GSE180895 | GEO

Anticancer Agent P-Bi-Tat Links The Thyroid Hormone Receptor On Integrin Αvβ3 To Cancer Cell Metabolism/Atp Generation [Suit2-P-biTAT]

Project description:Microarray analysis was carried out on human SUIT2 cells exposed to P-bi-TAT (10-6 M tetrac equivalent) for 24 h. P-bi-TAT significantly downregulated electron transport chain genes ATP5A1 (ATP synthase A1), ATP51, ATP5G2, COX6B1 (cytochrome c oxidase subunit 6B1), NDUFA8 (NADH dehydrogenase [ubiquinone] FA8), NDUFV2 and other NDUF genes, SLC25A6 (solute carrier group 2), UCP2 ([mitochondrial] uncoupling protein 2) and COX5A. The NDUF and ATP genes are also relevant to control of oxidative phosphorylation and transcription. Six additional NDUF genes linked to oxidative phosphorylation were affected. Conclusions. P-bi-TAT caused downregulation of expression of a panel of genes involved in electron transport, oxidative phosphorylation, and cytoplasmic ribosomal protein generation in GBM cells. A key component of the anticancer activity of P-bi-TAT relates to disordering of ATP generation mechanisms in tumor cells.

2022-04-27 | GSE180896 | 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