English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria

Matic, S., Jiang, M., Nicholls, T. J., Uhler, J. P., Dirksen-Schwanenland, C., Polosa, P. L., et al. (2018). Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria. Nat Commun, 9(1), 1202. doi:10.1038/s41467-018-03552-x.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0004-7211-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-73AA-B
Genre: Journal Article

Files

show Files

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Matic, S.1, Author
Jiang, M.1, Author
Nicholls, T. J.1, Author
Uhler, J. P.1, Author
Dirksen-Schwanenland, C.1, Author
Polosa, P. L.1, Author
Simard, M. L.1, Author
Li, X.1, Author
Atanassov, I.1, Author
Rackham, O.1, Author
Filipovska, A.1, Author
Stewart, J. B.1, Author
Falkenberg, M.1, Author
Larsson, N. G.1, Author
Milenkovic, D.1, Author
Affiliations:
1Department Larsson, Max Planck Institute for Biology of Ageing, Max Planck Society, Joseph-Stelzmann-Str. 9b, D-50931 Cologne, DE, ou_1942286              

Content

show
hide
Free keywords: -
 Abstract: 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.

Details

show
hide
Language(s):
 Dates: 2018-03-232018
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: Other: 29572490
DOI: 10.1038/s41467-018-03552-x
ISSN: 2041-1723 (Electronic)2041-1723 (Linking)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Nat Commun
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 9 (1) Sequence Number: - Start / End Page: 1202 Identifier: -