“The human body,” Morpheus tells Neo in the first of the Matrix movies, “generates more bioelectricity than a 120-volt battery.” No wonder the alien machine creatures in those movies see humans as a convenient source of cheap power.
In fact, there’s only enough electrical energy buzzing around your body to power an 80-watt light 
bulb, but Hollywood’s never let the truth get in the way of a good story, especially if it gives them an excuse to show a naked, bald Keanu Reeves extracting a three-pin plug from the back of his brain on screen.
There may not be enough energy in your body to make you a future alternative to fossil fuels (that’s a relief), but have you ever wondered where the energy that is there comes from? The story is almost as unlikely as the plot of The Matrix, but it’s true, and it has a lot to do with the long-term side effects of HIV treatment.
The human body is made up of billions and billions of cells. At the centre of each cell is a special compartment called the nucleus, which stores threads of DNA, the genetic material from which humans, and most living things are made. These threads of DNA are called chromosomes, there are 46 of them in each cell, and each chromosome contains between 50,000 and 100,000 a class=“glossary-term” href=”/glossary/term/126”>genes, which make up the genetic blueprint which determines our physical characteristics (hair colour, race, gender, whether you can touch the tip of your nose with your tongue, etc) and contain all the instructions needed to make our bodies develop and run.
The nucleus of the cell sits inside a surrounding cytoplasm, a jelly-like substance that also contains tiny, rod-like mitochondria which provide energy to the cell, by processing the chemicals absorbed from food (protein, fat and carbohydrate). Without these mitochondria, cells can’t do any of the work they’re designed to do — muscle cells can’t move, liver cells can’t remove impurities from the blood, brain cells can’t think.
It’s the prehistoric origin of these mitochondria that sounds like a plot from science fiction. A very long time ago, before the evolution of multi-celled organisms of earth, our very very distant ancestors were single-celled creatures, like bacteria. Many scientists now believe that the evolution of mitochondria was a key development that allowed multi-celled creatures to evolve — and it started with one bacterium engulfing another.
That engulfed bacterium evolved to become the mitochondria in our cells today; the ‘engulfer’ evolved to become us.
Because mitochondria are outside the nucleus, they are inherited entirely from the mother (the DNA inside your nucleus comes half from your mum and half from your dad). This has led scientists to describe this first single-celled, mitochondria-containg ancestor of ours as “mitochondrial Eve”.
All of the cells in your body today are descendants of mitochondrial Eve, a symbiotic relationship between two unrelated organisms, back in the primordial goo. It’s even possible to argue that mitochondria aren’t “us” at all, but (despite billions of years of shared history) an alien creature that has found a niche for itself inside our cells. In fact, due to its separate heritage, the mitochondrial DNA sequence is entirely different to the DNA inside our nucleus.
It sounds like a crazy idea, and it’s not universally accepted by scientists, but this theory of the origin of life, first proposed by Russian botanist Constantin Mereschkowsky in 1905, provides an intriguing idea of where the various components of our cells originated.
They may be hitchhikers inside our cells, but because they provide the energy for all the various processes inside our body, mitochondria are welcome — in fact essential — intruders.
As people age, get certain infections, or take certain drugs, changes can occur in mitochondria which make them produce less energy or stop working altogether. It’s this mitochondrial damage which lies at the heart of some of the most challenging long-term side effects of HIV treatment.
As they swim around inside our cells, mitochondria need an enzyme called polymerase gamma to reproduce. The nucleoside analogue class of antiretrovirals (AZT, 3TC, ddI, ddC, d4T, FTC and abacavir) is designed to block the enzyme reverse transcriptase, which HIV needs to reproduce. But the drugs in this class also interfere with polymerase gamma, to varying degrees, and can result in fewer mitochondria in our cells, or damaged mitochondria which don’t work properly.
The ‘d’ drugs — ddI, ddC and d4T — are believed to be the worst offenders in this regard, based on test-tube studies. In human studies, research has confirmed that people taking nucleoside analogue drugs, especially the ‘d’ drugs, seem to have fewer mitochondria inside their cells. Some research has also suggested that protease inhibitors can cause mutations in mitochondrial DNA.
Researchers have also found that people with HIV lipodystrophy, a side effect attributed to mitochondrial toxicity, have fewer mitochondria compared with people on treatment who don’t have lipodystrophy.
Lipodystrophy (wasting or redistribution of body fat) is just one of a raft of side effects which are now believed to be related, at least in part, to mitochondrial damage. Because the nucleoside analogue class of drugs is the oldest, and because most people on antiretroviral therapy take at least one drug from this class, many of these side effects have been around for years.
Along with lipodystrophy, myopathy (muscle wasting), peripheral neuropathy (numbness, tingling and pain in the toes and fingers) and pancreatitis (severe inflammation of the pancreas) are among the most well known side effects attributed to mitochondrial toxicity. Blood abnormalities such as thrombocytopenia (low platelets), a class=“glossary-term” href=”/glossary/term/402”>anaemia (low red blood cells) and neutropenia (low levels of neutrophils, a type of white blood cell) are all linked to mitochondrial toxicity and have all been around since the earliest days of HIV treatment.
More recently we have seen the arrival of other mitochondrial side effects, including lactic acidosis (a rare but potentially life-threatening condition in which high levels of lactate, a by-product of the process by which mitochondria convert sugar into energy, accumulate in the blood) and hepatic steatosis (also called “fatty liver”).
Because of the importance of mitochondria to the functioning of our bodies, and the likelihood that as people take antiretrovirals for longer periods of time the range of long-term side effects will increase, this list is likely to grow, at least until better HIV drugs are developed.
To avoid mitochondrial toxicity, there are a few things we can do. The most important is to have regular health monitoring including blood tests to ensure that any problems are diagnosed early. All of the various forms of mitochondrial toxicity respond well to strategies including treatment breaks, dose reductions and changes in treatment, as long as they are diagnosed early.
Some research has suggested that antioxidants, such as vitamins A, C and E, co-enzyme Q10, and the amino acid acetyl l-carnitine can help prevent mitochondrial toxicity. Some of these supplements can be expensive, and they can sometimes interfere with absorption of medication, so it’s important to discuss taking these with your doctor or other health care advisor before adding them to your treatment regime.
