PXD021639

PXD021639 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial proteome from liver and intestinal organoids from WT, Nrf2 knockout and Keap1 knockdown mice
Description	Transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) and its main negative regulator, Kelch-like ECH associated protein 1 (Keap1), are at the interface between redox and intermediary metabolism, allowing adaptation and survival under conditions of oxidative, inflammatory and metabolic stress. Nrf2 is the principal determinant of redox homeostasis, and contributes to mitochondrial function and integrity, and cellular bioenergetics. Using proteomics and lipidomics, we show that genetic downregulation of Keap1 in mice, and the consequent Nrf2 activation to pharmacologically-relevant levels, leads to upregulation of carboxylesterase 1 (Ces1) and acyl-CoA oxidase 2 (Acox2), decreases triglycerides levels, and alters the lipidome. This is accompanied by downregulation of hepatic ATP-citrate lyase (Acly) and decreased levels of acetyl-CoA, a trigger for autophagy. These findings suggest that downregulation of Keap1 confers features of a fasted metabolic state, which is an important consideration in the drug development of Keap1-targeting pharmacologic Nrf2 activators.
HostingRepository	PRIDE
AnnounceDate	2020-11-11
AnnouncementXML	Submission_2020-11-11_09:14:59.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mike Tatham
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-23 02:28:00	ID requested
⏵ 1	2020-11-11 09:15:00	announced

Dataset with its publication pending

submitter keyword: Nrf2, Keap1, mitochondrial, mouse, liver, organoids

Ronald Thomas Hay
contact affiliation	Professor of Molecular Biology. Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee ,Dundee, DD1 5EH, Scotland, UK
contact email	r.t.hay@dundee.ac.uk
lab head
Mike Tatham
contact affiliation	University of Dundee
contact email	m.tatham@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021639
     1. Label: PRIDE project
     2. Name: Mitochondrial proteome from liver and intestinal organoids from WT, Nrf2 knockout and Keap1 knockdown mice