PXD009138

PXD009138 is an original dataset announced via ProteomeXchange.

Title	Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria
Description	Replication of mammalian mitochondrial DNA (mtDNA) is an essential process that requires high fidelity and control at multiple levels to ensure proper mitochondrial function. Mutations in the mitochondrial genome maintenance exonuclease 1 (MGME1) gene were recently reported in mitochondrial disease patients. Here, to study disease pathophysiology, we generated Mgme1 knockout mice and report that homozygous knockouts develop depletion and multiple deletions of mtDNA. The mtDNA replication stalling phenotypes vary dramatically in different tissues of Mgme1 knockout mice. Mice with MGME1 deficiency accumulate a long linear subgenomic mtDNA species, similar to the one found in mtDNA mutator mice, but do not develop progeria. This finding resolves a long-standing debate by showing that point mutations of mtDNA are the main cause of progeria in mtDNA mutator mice. We also propose a role for MGME1 in the regulation of replication and transcription termination at the end of the control region of mtDNA.
HostingRepository	PRIDE
AnnounceDate	2018-07-11
AnnouncementXML	Submission_2018-07-11_05:47:39.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xinping Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-08 01:47:52	ID requested
⏵ 1	2018-07-11 05:47:40	announced

Matic S, Jiang M, Nicholls TJ, Uhler JP, Dirksen-Schwanenland C, Polosa PL, Simard ML, Li X, Atanassov I, Rackham O, Filipovska A, Stewart JB, Falkenberg M, Larsson NG, Milenkovic D, Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria. Nat Commun, 9(1):1202(2018) [pubmed]

curator keyword: Biological

submitter keyword: MGME1 knock out, mtDNA deletions, progeria

Xinping Li
contact affiliation	Max-Planck-Institute for Biology of Ageing, Germany
contact email	xli@age.mpg.de
lab head
Xinping Li
contact affiliation	Max Planck Institute for Biology of Ageing
contact email	xli@age.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/07/PXD009138

PRIDE project URI

• PRIDE
  1. PXD009138
     1. Label: PRIDE project
     2. Name: Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria