PXD012743

PXD012743 is an original dataset announced via ProteomeXchange.

Title	Pptc7 is an essential phosphatase for promoting mammalian mitochondrial metabolism and biogenesis
Description	Mitochondrial proteins are replete with phosphorylation; however, the origin, abundance, and functional relevance of these modifications are largely unclear. Nonetheless, mitochondria possess multiple resident phosphatases, suggesting that protein dephosphorylation may be broadly important for mitochondrial activities. To explore this, we deleted the poorly characterized matrix phosphatase Pptc7 from mice using CRISPR-Cas9 technology. Strikingly, Pptc7-/- mice exhibited marked hypoketotic hypoglycemia, elevated acylcarnitines, and lactic acidosis, and died soon after birth. Pptc7-/- tissues had significantly diminished mitochondrial size and protein content despite normal transcript levels, but consistently elevated phosphorylation on select mitochondrial proteins. These putative Pptc7 substrates include the protein translocase complex subunit Timm50, whose phosphorylation reduced import activity. We further find that phosphorylation in or near the mitochondrial targeting sequences of multiple proteins can disrupt their import rates and matrix processing. Overall, our data define Pptc7 as a protein phosphatase essential for proper mitochondrial function and biogenesis during the extrauterine transition. Natalie M Niemi, Gary M Wilson, Katherine A Overmyer, F.-Nora Vogtle, Danielle C Lohman, Kathryn L Schueler, Alan D Attie, Chris Meisinger, Joshua J Coon, David J Pagliarini. (2018) “Pptc7 is an essential phosphatase for promoting mammalian mitochondrial metabolism and biogenesis.” biorx: https://doi.org/10.1101/426247
HostingRepository	PRIDE
AnnounceDate	2019-05-29
AnnouncementXML	Submission_2019-07-29_01:06:24.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gary Wilson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-18 01:21:53	ID requested
1	2019-05-29 00:56:41	announced
⏵ 2	2019-07-29 01:06:25	announced	Updated publication reference for PubMed record(s): 31324765.

Niemi NM, Wilson GM, Overmyer KA, V, ö, gtle FN, Myketin L, Lohman DC, Schueler KL, Attie AD, Meisinger C, Coon JJ, Pagliarini DJ, Pptc7 is an essential phosphatase for promoting mammalian mitochondrial metabolism and biogenesis. Nat Commun, 10(1):3197(2019) [pubmed]

curator keyword: Biological

submitter keyword: Pptc7, Mitochondia, Phosphoproteome

Joshua J. Coon
contact affiliation	University of Wisconsin-Madison
contact email	jcoon@chem.wisc.edu
lab head
Gary Wilson
contact affiliation	UW-Madison
contact email	gwilson9@wisc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012743
     1. Label: PRIDE project
     2. Name: Pptc7 is an essential phosphatase for promoting mammalian mitochondrial metabolism and biogenesis