Mechanism Developed to Manipulate Oxidative Stress Using Glutathione Transporter Could Destroy Cancer Cells

It is quite sad that with the privilege of life, comes the inevitability of death. The vital processes for our daily living, are surprisingly overlooked deadly processes in our bodies. The mitochondria, which is the site of major chemical reactions for our cells, which form various systems, produce toxic free radicals during these processes. These free radicals can lead to cancer, cardiovascular diseases, nervous system malfunction, etc. when they are in large amounts. This means that the hustle and bustle of body systems going about their business is eventually what kills us.

Mitochondria

Mitochondria

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Study results

Unsurprisingly, the body saves itself from deteriorating as it produces antioxidants to neutralize the chemical effect of these free radicals produced during oxidative phosphorylation and other metabolic processes. The antioxidant effect neutralizes the damaging effects of the free radicals. Harmful as they may be, the effect of these free radicals could be studied and applied in the management of diseases.

Birsoy and his team of Rockefeller scientists, in their study, found the transporter of glutathione. Glutathione is a major antioxidant for free radicals in the body. Finding its transporter is a major step forward as this transporter can control the amount of glutathione taken into the mitochondria. Note that glutathione is not produced inside the mitochondria but in the cell’s cytosol. This means that by manipulating the production level of the transporter, we can create any free radical concentration we desire in the mitochondria’s environment.

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This transporter, SLC25A39 protein, holds an entangled relationship with glutathione. This SLC25A39 protein is one of those hitherto unknown yet very important constituents for the body. The production of this transporter is dependent on the amount of glutathione available. This relationship is indirect; a decrease in glutathione results in the production of more transport protein. This is simply because with low glutathione levels, there is a higher chance of oxidative stress and the body defends itself by producing more shuttles to transport glutathione into the mitochondria for balance. However, a blockage of this same protein led to reduced amounts of glutathione only inside the mitochondria and not in the cell’s cytosol. This led to the rapid death of red blood cells by oxidative stress, thereby leading to the death of the experiment subject (mice).

Clinical significance

From a clinical perspective, this advance could be used to prevent glutathione from entering the mitochondria of tumor cells, thereby inducing oxidative stress. This could be a novel way to manage cancer with maximal efficiency. This discovery of the protein shuttle births a miracle, and realization of different pathways for different diseases caused by oxidative stress. This provides a new approach and hope for more specific and correct diagnosis and drug targets for related diseases involving aging and neurodegeneration.

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Conclusion

From the words of Birsoy, “ Related diseases can be prevented or treated by fighting the cell’s defense which involves inducing oxidative stress.” Finding solutions to diseases has always been a battle we’ve fought from without, but the more successful way may very well be from within.

References

SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells

 

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