PXD006293-2

PXD006293 is an original dataset announced via ProteomeXchange.

Title	Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals
Description	Mitonuclear communication is essential to maintain cellular and organismal homeostasis in equilibrium and stress. Mitochondrial stress activates a concerted mitonuclear response geared to safeguard and repair mitochondrial function and to adapt cellular metabolism to the stress. However, the common mediator driving this stress response in mammals remains elusive. By using a multi-omics approach we identify that the activating transcription factor 4 (ATF4) is the main player regulating this response. ATF4 activates the expression of cytoprotective genes, which reprogram cellular metabolism, through activation of the integrated stress response (ISR). Mitochondrial stress also promotes a local proteostatic response, by inducing a decrease in mitochondrial ribosomal proteins, inhibiting mitochondrial translation and coupling as such the activation of the ISR with the attenuation of mitochondrial function. Our data illustrate the value of a multi-omics approach to characterize complex cellular networks and provide a versatile resource to identify new regulators of mitochondrial-related diseases.
HostingRepository	PRIDE
AnnounceDate	2017-06-01
AnnouncementXML	Submission_2017-06-07_00:18:59.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Miguel Prado
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-04-13 06:51:48	ID requested
1	2017-06-01 06:04:19	announced
⏵ 2	2017-06-07 00:19:00	announced	Updated publication reference for PubMed record(s): 28566324.

Quir, ó, s PM, Prado MA, Zamboni N, D'Amico D, Williams RW, Finley D, Gygi SP, Auwerx J, Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals. J Cell Biol, 216(7):2027-2045(2017) [pubmed]

curator keyword: Biological

submitter keyword: mitochondria, ATF4, omics, human, Orbitral Fusion

Daniel J Finley
contact affiliation	Finley and Gygi lab Cell Biology Department Harvard Medical School US
contact email	daniel_finley@hms.harvard.edu
lab head
Miguel Prado
contact affiliation	Harvard Medical School
contact email	miguel_prado@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006293
     1. Label: PRIDE project
     2. Name: Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals