Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development.
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.
Faculty of Life and Environmental Sciences,  University of Tsukuba, Tsukuba, Ibaraki 305-8572,  Japan.
Osamu
O
Hashizume
Akinori
A
Shimizu
Mutsumi
M
Yokota
Atsuko
A
Sugiyama
Kazuto
K
Nakada
Hiroyuki
H
Miyoshi
Makiko
M
Itami
Miki
M
Ohira
Hiroki
H
Nagase
Keizo
K
Takenaga
Jun-Ichi
J
Hayashi
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D028361:Mitochondrial Diseases / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism
D017931:DNA Primers; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species