PXD020262

PXD020262 is an original dataset announced via ProteomeXchange.

Title	Genetic regulation of the ATP synthase in neurons modulates cognition
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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:22:15.124.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD020262
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Pau B. Esparza-Molto
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iTRAQ8plex-116 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-08 06:36:35	ID requested
1	2021-05-24 13:58:30	announced
⏵ 2	2024-10-22 05:22:16	announced	2024-10-22: Updated project metadata.

Esparza-Molt, ó PB, Romero-Carrami, ñ, ana I, N, ú, ñ, ez de Arenas C, Pereira MP, Blanco N, Pardo B, Bates GR, S, á, nchez-Castillo C, Artuch R, Murphy MP, Esteban JA, Cuezva JM, Generation of mitochondrial reactive oxygen species is controlled by ATPase inhibitory factor 1 and regulates cognition. PLoS Biol, 19(5):e3001252(2021) [pubmed]

10.1371/journal.pbio.3001252;

10.6019/PXD020262;

submitter keyword: hippocampus,Mouse, iTRAQ

Jose M. Cuezva
contact affiliation	Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid
contact email	jmcuezva@cbm.csic.es
lab head
Pau B. Esparza-Molto
contact affiliation	Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid
contact email	pbesparza@cbm.csic.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020262
     1. Label: PRIDE project
     2. Name: Genetic regulation of the ATP synthase in neurons modulates cognition