Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development.

Abstract

It has been hypothesized that respiration defects caused by accumulation of pathogenic mitochondrial DNA (mtDNA) mutations and the resultant overproduction of reactive oxygen species (ROS) or lactates are responsible for aging and age-associated disorders, including diabetes and tumor development. However, there is no direct evidence to prove the involvement of mtDNA mutations in these processes, because it is difficult to exclude the possible involvement of nuclear DNA mutations. Our previous studies resolved this issue by using an mtDNA exchange technology and showed that a G13997A mtDNA mutation found in mouse tumor cells induces metastasis via ROS overproduction. Here, using transmitochondrial mice (mito-mice), which we had generated previously by introducing G13997A mtDNA from mouse tumor cells into mouse embryonic stem cells, we provide convincing evidence supporting part of the abovementioned hypothesis by showing that G13997A mtDNA regulates diabetes development, lymphoma formation, and metastasis--but not aging--in this model.

• Authors: Osamu Hashizume, Akinori Shimizu, Mutsumi Yokota, Atsuko Sugiyama, Kazuto Nakada, Hiroyuki Miyoshi, Makiko Itami, Miki Ohira, Hiroki Nagase, Keizo Takenaga, Jun-Ichi Hayashi
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 109 Issue 26 Pg. 10528-33 (Jun 26 2012) ISSN: 1091-6490 [Electronic] United States
• PMID: 22689997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• DNA, Mitochondrial
• Reactive Oxygen Species

Topics

• 3T3 Cells
• Animals
• Base Sequence
• Cell Line, Transformed
• DNA Primers
• DNA, Mitochondrial (genetics)
• Diabetes Mellitus, Experimental (genetics)
• Lymphoma (genetics)
• Mice
• Mitochondrial Diseases (genetics)
• Mutation
• Phenotype
• Polymerase Chain Reaction
• Reactive Oxygen Species (metabolism)