Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The inhibitor protein IF1 from mammalian mitochondria inhibits ATP hydrolysis but not ATP synthesis by the ATP synthase complex

ABSTRACT: The hydrolytic activity of the ATP synthase in bovine mitochondria is inhibited by a protein called IF1, but bovine IF1 has no effect on the synthetic activity of the bovine enzyme in mitochondrial vesicles in the presence of a proton motive force. As part of an investigation into the inhibitory effects on the hydrolytic and synthetic activities of ATP synthase in bovine sub-mitochondrial particles, the absolute quantities of both the ATP synthase complex and the IF1 protein have been measured.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Bos Taurus (bovine)

TISSUE(S): Heart

SUBMITTER: Ian M. Fearnley

LAB HEAD: John E. Walker

PROVIDER: PXD045079 | Pride | 2024-01-29

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	CAR4566A3MA2JC-BHSMPQ-A1-191127-SJD.msf	Msf
	CAR4566A3MA2JC-BHSMPQ-A1-191127-SJD.raw	Raw
	CAR4566A3MA3JC-BHSMPQ-A1-191127-SJD.msf	Msf
	CAR4566A3MA3JC-BHSMPQ-A1-191127-SJD.raw	Raw
	CAR4566A4MA2JC-BHSMPQ-B1-191127-SJD.msf	Msf

Items per page:

1 - 5 of 11

Publications

The inhibitor protein IF1 from mammalian mitochondria inhibits ATP hydrolysis but not ATP synthesis by the ATP synthase complex.

Carroll Joe J Watt Ian N IN Wright Charlotte J CJ Ding Shujing S Fearnley Ian M IM Walker John E JE

The Journal of biological chemistry 20240126 3

The hydrolytic activity of the ATP synthase in bovine mitochondria is inhibited by a protein called IF1, but bovine IF1 has no effect on the synthetic activity of the bovine enzyme in mitochondrial vesicles in the presence of a proton motive force. In contrast, it has been suggested based on indirect observations that human IFI inhibits both the hydrolytic and synthetic activities of the human ATP synthase and that the activity of human IF1 is regulate ...[more]

PMID: 38280428

Similar Datasets

Genetic regulation of the ATP synthase in neurons modulates cognition

Project description:The goal of this analysis was to profile the gene expression signatures associated to different neuronal doses of IF1. The mitochondrial ATP synthase produces ATP by oxidative phosphorylation and integrates different signals to regulate cellular functions and fate. The ATPase inhibitory factor 1 (IF1) is a structurally-disordered protein that inhibits the ATP synthase, contributing to metabolic reprogramming and signalling through mitochondrial reactive oxygen species (mtROS). mtROS regulate kinases and transcription factors in mitohormetic responses that favour adaptation to toxic insults. IF1 is tissue-specifically expressed and in human and mouse brain is in molar excess over the ATP synthase. Herein, we have used genetic approaches to ablate or overexpress IF1 in neurons to investigate its role in brain functions. IF1 inhibits a fraction of the ATP synthase under physiological conditions and regulates respiration, mtROS production and mitochondrial structure. Transcriptomic, proteomic and metabolomic analyses indicate that IF1 regulates synaptic transmission and cognition. Ablation of IF1 impairs short-term memory whereas IF1 overexpression increases basal synaptic transmission and learning by mtROS-dependent activation of the extracellular signal-regulated kinases 1/2 (ERK 1/2). Overall, we show that IF1 dose plays a fundamental role in the regulation of neuronal function by controlling the fraction of inhibited ATP synthase that acts as source of mitohormetic mtROS, further emphasizing the ATP synthase/IF1 as promising targets to treat cognitive disorders.

2021-05-24 | GSE154064 | GEO

Genetic regulation of the ATP synthase in neurons modulates cognition

Project description:The mitochondrial ATP synthase produces ATP by oxidative phosphorylation and integrates different signals to regulate cellular functions and fate. The ATPase inhibitory factor 1 (IF1) is a structurally-disordered protein that inhibits the ATP synthase, contributing to metabolic reprogramming and signalling through mitochondrial reactive oxygen species (mtROS). mtROS regulate kinases and transcription factors in mitohormetic responses that favour adaptation to toxic insults2. IF1 is tissue-specifically expressed and in human and mouse brain is in molar excess over the ATP synthase. Herein, we have used genetic approaches to ablate or overexpress IF1 in neurons to investigate its role in brain functions. IF1 inhibits a fraction of the ATP synthase under physiological conditions and regulates respiration, mtROS production and mitochondrial structure. Transcriptomic, proteomic and metabolomic analyses indicate that IF1 regulates synaptic transmission and cognition. Ablation of IF1 impairs short-term memory whereas IF1 overexpression increases basal synaptic transmission and learning by mtROS-dependent activation of the extracellular signal-regulated kinases 1/2 (ERK 1/2). Overall, we show that IF1 dose plays a fundamental role in the regulation of neuronal function by controlling the fraction of inhibited ATP synthase that acts as source of mitohormetic mtROS, further emphasizing the ATP synthase/IF1 as promising targets to treat cognitive disorders.

2021-05-24 | PXD020262 | Pride

Proteomic analysis of highly purified bovine F0F1 ATP Synthase

Project description:We performed a proteomic analysis of highly purified bovine F0F1 ATP synthase to assess the quality of the purification procedure adopted to isolate the protein complex and identify possible contaminant proteins.

2019-09-25 | PXD015108 | Pride

Trypanosoma brucei bloodstream form mitochondrion is capable of ATP production by substrate-level phoshorylation

Project description:The bloodstream form Trypanosoma brucei maintains its essential mitochondrial membrane potential (ΔΨm) through the proton-pumping activity of the FoF1-ATP synthase operating in the reverse mode. The ATP that drives this hydrolytic reaction has long been thought to be generated by glycolysis and imported from the cytosol via an ATP/ADP carrier (AAC). Indeed, we demonstrate that AAC is the only carrier that can import ATP into the mitochondrial matrix to power the hydrolytic activity of the FoF1-ATP synthase. However, contrary to expectations, the deletion of AAC has no effect on parasite growth, virulence or levels of ΔΨm. This suggests that ATP is produced by substrate-level phosphorylation pathways in the mitochondrion. Therefore, we knocked out the succinyl-CoA synthetase (SCS) gene, a key mitochondrial enzyme that produces ATP through substrate-level phosphorylation in this parasite. Its absence resulted in changes to the metabolic landscape of the parasite, lowered virulence, and reduced mitochondrial ATP content. Strikingly, these SCS mutant parasites become more dependent on AAC as demonstrated by a 25-fold increase in their sensitivity to the AAC inhibitor, carboxyatractyloside. Since the parasites were able to adapt to the loss of SCS in culture, we also analyzed the more immediate phenotypes that manifest when SCS expression is rapidly suppressed by RNAi. Importantly, when performed under nutrient-limited conditions mimicking various host environments, SCS depletion strongly affected parasite growth and levels of ΔΨm. In totality, the data establish that the bloodstream form mitochondrion is capable of generating ATP via substrat-level phosphorylation pathways.

2024-01-26 | PXD044938 | Pride

Gene expression analysis in 13 patients with mitochondrial ATP synthase deficiency (Agilent)

Project description:Defects of mitochondrial functions lead in humans to vast array of usually multisystemic pathologies and several hundreds of diseases resulting from various defects of mitochondria biogenesis and maintenance, defects of respiratory chain complexes (OXPHOS) or defects of individual mitochondrial proteins are known. We used Agilent Whole Human Genome Microarray for gene expression profiling of genetically heterogeneous group of 13 patients with biochemically proven ATP synthase deficiency. Gene expression data analysis allowed classification of patients into several distinct groups, provided information on subgroup and patient specific gene expression profiles, defined candidate disease causing genes and gave basic information on pathogenic mechanisms associated with ATP synthase deficiency. Keywords: ATP synthase, mitochondrial biogenesis, ROS, gene expression, microarray, human Two-condition experiment, patients vs. controls cells. Biological replicates: 9 control, 13 patients, independently grown and harvested.

2008-08-01 | E-GEOD-10956 | biostudies-arrayexpress

ACE-Scan of the ATP RNA aptamer on 10^12 Gen1 DNA microarray

Project description:The experiments were carried out to map the ligand binding landscape of various DNA and RNA duplexed aptamer families. Duplexed Aptamer (DA) constructs were engineered from (i) natural and synthetic DNA and RNA aptamers and (i) synthetic oligonucleotide aptamer-complementary elements synthesized on custom DNA microarrays. The aptamers tested consist of the ATP DNA aptamer, the ATP RNA aptamer, the cocaine DNA aptamer, the human alpha-thrombin DNA aptamer, and the natural add riboswitch aptamer from the pathogenic bacteria Vibrio vulnificus. Each duplexed aptamer family consists of 1000's of synthetic constructs, each formed by hybridizing the aptamer with an aptamer-complementary element (ACE) - here, ACEs consisted of various DNA oligonucleotides synthesized as a custom DNA microarray.

2017-12-20 | E-MTAB-6376 | biostudies-arrayexpress

Apoptolidin family glycomacrolides target leukemia through inhibition of ATP synthase

Project description:Cancer cells have long been recognized to exhibit unique bioenergetic requirements. The apoptolidin family of glycomacrolides are distinguished by their selective cytotoxicity towards oncogene transformed cells, yet their molecular mechanism remains uncertain. We used photoaffinity analogs of the apoptolidins to identify the F1 subcomplex of mitochondrial ATP synthase as the target of apoptolidin A. CryoEM of apoptolidin and ammocidin-ATP synthase complexes revealed a novel shared mode of inhibition that was confirmed by deep mutational scanning of the binding interface to reveal resistance mutations which were confirmed using CRISPR-Cas9. Ammocidin A was found to suppress leukemia progression in vivo at doses that were tolerated with minimal toxicity. These studies reveal that OXPHOS dependent cancers are vulnerable to ATP synthase inhibition by apoptolidin family glycomacrolides compounds.

2021-05-31 | GSE171362 | GEO

ACE-Scan of the ATP DNA aptamer on 10^12 density Gen1 DNA microarray

2017-12-20 | E-MTAB-6374 | biostudies-arrayexpress

ACE-Scan of the ATP DNA aptamer on various density Gen2 DNA microarrays

2017-12-20 | E-MTAB-6375 | biostudies-arrayexpress

Gene expression analysis in 13 patients with mitochondrial ATP synthase deficiency (Agilent)

2008-08-01 | GSE10956 | GEO