Dataset Information

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

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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Xinping Li

LAB HEAD: Xinping Li

PROVIDER: PXD009138 | Pride | 2018-07-11

REPOSITORIES: Pride

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			Action	DRS
	161014_FS1_Li_Caren_B1.raw	Raw
	161014_FS1_Li_Caren_B2.raw	Raw
	161014_FS1_Li_Caren_B3.raw	Raw
	161014_FS1_Li_Caren_M1.raw	Raw
	161014_FS1_Li_Caren_M2.raw	Raw

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

Matic Stanka S Jiang Min M Nicholls Thomas J TJ Uhler Jay P JP Dirksen-Schwanenland Caren C Polosa Paola Loguercio PL Simard Marie-Lune ML Li Xinping X Atanassov Ilian I Rackham Oliver O Filipovska Aleksandra A Stewart James B JB Falkenberg Maria M Larsson Nils-Göran NG Milenkovic Dusanka D

Nature communications 20180323 1

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 stallin ...[more]

PMID: 29572490

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