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AIDS InfoNet www.aidsinfonet.org Fact Sheet Number 556 MITOCHONDRIAL TOXICITY WHAT ARE MITOCHONDRIA? before the blood test – including Different medications build up in Mitochondria (my-toe-con´-dree-a) are climbing stairs or walking quickly – can different parts of the body. This could small “organs” in our cells. They are increase lactic acid levels and throw off explain how MT caused by different the cell’s power plant. They use the test results. drugs can lead to side effects in oxygen, fat and sugar to produce different parts of the body. adenosine triphosphate (ATP). This It’s difficult to know if you have MT. process is called “cellular respiration.” Usually the symptoms of lactic acidosis We know that MT can cause muscle When the cell needs energy, it breaks increase very gradually over a long weakness in people taking AZT. It is down molecules of ATP to release the period of time. However, you can look probably the cause of “fatty liver” stored energy. for the following signs of lactic acidosis: (hepatic steatosis) and high levels of  Nausea lactic acid that can be caused by all of The more energy the cell needs, the  Vomiting the nukes. Unfortunately, there is very more mitochondria it contains. One cell  Severe fatigue little research on how much can have anywhere from a few  Recent weight loss mitochondrial damage each ARV mitochondria up to thousands. The  Rapid, deep breathing causes to different parts of the body. highest numbers are found in nerve,  Cramps, muscle aches and We also don’t know which muscle, and liver cells. numbness or tingling combinations of drugs cause the most MT.  Muscle weakness that rapidly gets Some scientists believe that worse mitochondria may be the key to aging. Researchers know how to measure the number of mitochondria in different As we grow older, our mitochondria Lactic acidosis can be fatal. See cells, compared to normal. However, collect more and more mutations. your health care provider they don’t know many mitochondria a immediately if you have these cell can lose before there are symptoms. WHAT IS MITOCHONDRIAL problems. TOXICITY? MT may also cause nerve damage Mitochondrial toxicity (MT) is damage (peripheral neuropathy, see Fact Sheet that decreases the number of 555). It has been linked to kidney mitochondria. If there are too few damage and hearing loss. Some BOTTOM LINE mitochondria in a cell, it might stop researchers believe it might also Lactic acidosis is a rare side effect of working properly. It’s not clear how contribute to fat redistribution some HIV medications, especially the much loss of mitochondria can occur (lipodystrophy, see Fact Sheet 553) in older reverse transcriptase inhibitors. before there is loss of cell function. people taking antiretroviral medications (ARVs). People living with HIV and their health care providers need to recognize the symptoms of lactic acidosis, if ignored, WHAT ARE THE SIGNS OF lactic acidosis can be fatal. MT? HOW DO ARVs CAUSE MT? One of the most common signs of MT Mitochondria have an enzyme that is muscle weakness (myopathy). If helps them multiply. This enzyme is muscle cells can’t get enough energy called DNA polymerase gamma, or “pol through cellular respiration, they have gamma.” It is very similar to HIV’s to get energy without oxygen. This reverse transcriptase enzyme. “anaerobic” energy production creates Unfortunately, this also means that the lactic acid as a waste product. some drugs we use to inhibit reverse transcriptase can also inhibit pol Elevated levels of lactic acid can cause gamma. When this happens, fewer sore muscles. For example, the new mitochondria may be produced. soreness people feel after running a marathon is caused by a buildup of Some nucleoside analog reverse lactic acid. Some people with MT have transcriptase inhibitors (AZT, 3TC, ddI, very high levels of lactic acid in their d4T) inhibit pol gamma to some blood. This rare condition is called degree. MT is more likely to occur the lactic acidosis. There is a blood test for longer you take these drugs. lactic acid levels. Physical exertion

A Project of the International Association of Providers of AIDS Care. Fact Sheets can be downloaded from the Internet at http://www.aidsinfonet.org Revised September 5, 2014

A Project of the International Association of Providers of AIDS Care. Fact Sheets can be downloaded from the Internet at http://www.aidsinfonet.org