Mitochondrial DNA Shows Resistance to Mutagen Exposure
Jason Bielas, Ph.D.
Fred Hutchinson Cancer Research Center
Research, funded in part by NIEHS, showed that the high rates of DNA mutations seen in mitochondria do not arise from a sensitivity to damage or reduced repair capacity, as was previously thought to be the case. The new work suggests that mitochondria can prevent induced DNA damage from leading to mutations in the mitochondrial genetic code.
To study mitochondrial DNA mutations, the researchers examined the effects of benzo[a]pyrene (B[a]P), a combustion byproduct found in tobacco smoke and coal tar, and N ethyl N nitrosourea (ENU), which is known to induce mutations in the nuclear DNA of mice. After exposing mice to three different doses of B[a]P or one dose of ENU every day for 28 days, the researchers applied a technique they previously developed to precisely and accurately measure mutations in mitochondrial DNA.
The researchers found that after 4 weeks, none of the B[a]P or ENU doses had led to an increased rate of mutations in mitochondrial DNA from the liver or bone marrow. However, the frequency of mutations in nuclear DNA had risen significantly, from four to over 150 times the usual rate, depending on mutagen, dose, and tissue examined.
The researchers verified that B[a]P did cause DNA damage in the mitochondria even though they detected no changes in the sequence of mitochondrial DNA in exposed animals. These results demonstrate that induced mitochondrial DNA damage does not readily convert into mutations. More research is needed to better understand how mitochondria repress mutations after exposure to DNA-damaging agents.
Citation: Valente WJ, Ericson NG, Long AS, White PA, Marchetti F, Bielas JH. 2016. Mitochondrial DNA exhibits resistance to induced point and deletion mutations. Nucleic Acids Res 44(18):8513-8524.
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