Deletion-mutant mtDNA increases in somatic tissues but decreases in female germ cells with age.
The proportions of mutant and wild-type mtDNA are crucial in determining the severity of mitochondrial diseases. It has been generally considered that deletion-mutant mtDNA has replication advantages and accumulates with time. Here, we examine the tissue-by-tissue proportions of mutant mtDNA with a 4696-bp deletion (DeltamtDNA) and wild-type mtDNA in mitochondrial disease model mice (mito-mice). Comparison of the proportions of DeltamtDNA in each tissue at various ages showed that the rate of accumulation of DeltamtDNA differed among tissues. The heart, skeletal muscles, kidney, liver, testis, and ovary showed increases in the proportion of DeltamtDNA with age, but the pancreas, spleen, brain, and blood showed only a slight or no increase in proportion. In contrast to the somatic tissues, however, the germ cells of female mito-mice and resultant offspring showed a strong decrease in DeltamtDNA with maternal age. The decrease was so acute that some offspring showed complete disappearance of DeltamtDNA, even though their elder brothers and sisters had high proportions of DeltamtDNA. Female germ cells have a machinery that prevents the inheritance of defective mtDNA to the following generation since germ cells are kept for a long time until they are ovulated.
Sato
Akitsugu
A
Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan. asato@biol.tsukuba.ac.jp
Nakada
Kazuto
K
Shitara
Hiroshi
H
Kasahara
Atsuko
A
Yonekawa
Hiromichi
H
Hayashi
Jun-Ichi
J
D000375:Aging / Q000235:genetics*; D000818:Animals; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D050259:Genes, Mitochondrial; D005854:Germ Cells; D051379:Mice; D028361:Mitochondrial Diseases / Q000235:genetics*; D017384:Sequence Deletion; D014018:Tissue Distribution
D004272:DNA, Mitochondrial