Effects of Third Hand Smoke on Mitochondrial Genetic/Epigenetics and Their Inheritance Pattern
Abstracts
Initial Award Abstract |
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Third Hand Smoke (THS) is made of toxins that stick to fabric, carpet, and upholstery that have been exposed to cigarette smoke. Not all THS can be removed with household cleaners. Therefore, many people are unknowingly exposed to THS. Long term THS exposure causes metabolic problems. It has been shown that THS-exposed mice have lower energy in the form of the cell currency called ATP and increased triglycerides. When removed from THS, some symptoms return to normal by 6 months. Interestingly, symptoms of altered metabolism do not. This suggests that THS affects the part of the cell that regulates metabolism, the mitochondria. Mitochondria have its own DNA (mtDNA) that is separate from the rest of the DNA in the cell. We believe that metabolic stress is induced by THS due to changes in the mtDNA and that these changes can be inherited by offspring. These changes to mtDNA may be genetic mutations, or epigenetic changes. Epigenetic changes are changes to DNA that do not include changes to the sequence itself. One example is the addition of an extra molecule called a methyl group to the DNA, which can make a gene work less efficiently, much like DNA mutations might. We will investigate:
The effects of THS on genome and epigenome of mitochondria. Because many of the genes involved in metabolism are coded in the mitochondrial genome, we evaluate mtDNA for genetic and epigenetic changes. Early data has shown that mtDNA isolated from THS-exposed mice have more methylations. This may be contributing to decrease expression of genes needed by the mitochondria, resulting in lowered activity for the electron transport chain, which would result the lowered ATP that we have observed.
Investigate if the effects of THS are transgenerational. Because some changes remain altered after toxin exposure has stopped, it is possible that these alterations can be passed onto the offspring. Genetic mutations have been well established to be inherited. Epigenetic inheritance has only been recently observed and examples revolve around metabolic dysfunction in response to toxin exposure.
Our studies are novel because epigenetics of mtDNA has only been shown in small number of diseases. Our studies will help to understand of THS toxicity and whether it is passed on to the next generations, which will improve strategies for reversing the effects, impacting human health. |
