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.; Simard, M.-L.; Li, X.; Atanassov, I.; Rackham, O.; Filipovska, A.; Stewart, J.; Falkenberg, M.; Larsson, N.G.; Milenkovic, D.

doi:10.1038/s41467-018-03552-x

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学術論文

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

MPS-Authors

/persons/resource/persons129404

Matic, S.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278114

Jiang, M.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278394

Dirksen-Schwanenland, C.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons147295

Simard, M.-L.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons277927

Li, X.
Proteomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons104734

Atanassov, I.
Proteomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129358

Stewart, J.
Stewart – Mitochondrial Mutations and Genome Co-evolution, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129342

Larsson, N.G.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129408

Milenkovic, D.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/29572490
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引用

Matic, S., Jiang, M., Nicholls, T. J., Uhler, J. P., Dirksen-Schwanenland, C., Polosa, P. L., Simard, M.-L., Li, X., Atanassov, I., Rackham, O., Filipovska, A., Stewart, J., Falkenberg, M., Larsson, N., & Milenkovic, D. (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.

引用: https://hdl.handle.net/21.11116/0000-000B-47BB-3

要旨

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.