Drug-Induced Mitochondrial Toxicity

Mitochondrial Toxicity

Mitochondria are organelles, which are the equivalence of cells’ organs, that help carry out multiple processes of metabolism which include the breakdown, storage, and usage of fats, proteins, and carbs for the creation of energy. Cells are the smallest units in the body that make up tissues and are responsible for multiple functions involving metabolism. Mitochondria play an important role in cellular respiration, which is when food is consumed and combined with oxygen to create energy and allow the body to carry out functions. They are found in multiple cells, from muscle cells to immune cells, where disruptions in proper mitochondrial function could have negative effects on the cells and to the person. These disruptions were seen in previous medications used to treat HIV, known as the human immunodeficiency virus. This virus is spread through infected bodily fluids such as semen or blood and affects white blood cells, which are responsible for fighting infections from pathogens or foreign objects introduced into the body. The virus depletes these cells and makes the person more prone to infections, which could become life-threatening. Currently, all the therapies that exist treat the infection by preventing the virus from replicating and producing more viruses to infect other cells. None of the current medications cure the disease, meaning they do not completely remove the virus from the body. The older medications used to treat HIV would target the mitochondria of cells, which would lead to mitochondrial dysfunction and decline, known as mitochondrial toxicity.

Mitochondrial Toxicity and HIV Medications

Medications used to treat HIV also known as antiretroviral medications successfully prevent the virus from producing more viruses to infect other cells. However, the medications have to be taken long-term and could lead to disruptions in metabolism. As mentioned earlier, older HIV medications would prevent the virus from replicating but also affect the production of proteins and mitochondria products to carry out metabolic processes. This ultimately results in the cell dying and other clinical presentations such as muscle pains, kidney dysfunction, liver failure, etc. Although mitochondrial toxicity is common in older medications than the newer ones used to treat HIV, another adverse effect includes fat changes and fat distribution among the body -- known as lipodystrophy. Both in the older and newer medications affect the breakdown of fat and lead to dysregulations of fat levels within the body, which increases the person’s risk for heart attacks, strokes, and liver dysfunction. All of which is speculated to be a result of mitochondrial toxicity, which shows the important role that mitochondria have in the body.

References

Pérez-Matute P, Pérez-Martínez L, Blanco JR, Oteo JA. Role of mitochondria in HIV infection and associated metabolic disorders: focus on nonalcoholic fatty liver disease and lipodystrophy syndrome. Oxidative medicine and cellular longevity. 2013 Oct;2013. doi: 10.1155/2013/493413