In Depth

In Depth

Mitochondria - Even Mightier Than We Thought

By Jenifer Lienau Thompson

You may think that you are just sitting there reading, but right now your body is working pretty hard. Your heart pumps blood throughout your body, your diaphragm pulls air into your lungs, muscles in your back and abdomen hold your body up. Within your organs and tissues, cells cooperate to perform all these activities. Muscle cells expand and contract so your eyes can scan the screen, nerve cells transmit messages about these words to your brain, and brain cells works together to decipher their meanings. It actually takes a lot of energy to sit there and read - imagine how much it takes to ride a bike, turn a cartwheel or run a marathon!

Where do you get all the energy you need? Just as your mom has always told you, it begins with the food you eat. But a peanut butter and jelly sandwich (PB&J) is not exactly cell food - at least not yet. Your digestive system breaks the PB&J down into its molecular ingredients: proteins, sugars, and fats - and your blood vessels deliver them to cells throughout your body. Tiny power plants that look like little loaves of bread inside your cells, called mitochondria, combine the food molecules with oxygen to make ATP - an energy-storage molecule that acts like a rechargeable battery, providing energy for everything you do.

Two recent articles by Joe Miksch in PittMed magazine examine new developments in our understanding of mitochondria's mighty influence on human health. For a long time, scientists thought that mitochondria's sole purpose was to generate energy, but we now know that they do a lot more. Throughout your life, mitochondra (researchers sometimes call them "mitos" for short) copy the cellular energy production system perfectly, millions of times over. They also convince sick or damaged cells to die quickly and quietly. Pitt researchers think that these less-appreciated mitochondrial roles may unlock the mysteries of some devastating diseases like cancer and Parkinson's.

The problem seems to be rooted in how mitochondria replicate and produce energy. They actually have their own special DNA - a very short strand of it - which they continuously copy. Mitochondrial DNA (mtDNA) encodes the instructions on how to make proteins that convert food and oxygen into energu.

Imagine that you had to copy the same sentence over and over and over again, millions of times. You might make a spelling or grammar mistake once in a while. If you weren't paying attention, you might repeat the mistake. Eventually, the mistake could become a permanent part of your sentence. Sometimes mitochondria make mistakes, called mutations, when they copy their DNA. Mitos constantly fuse together and divide, fixing mistakes and throwing out faulty DNA that can't be repaired. But occasionally, mutations go undetected and get copied. When this happens in mitochondrial DNA (mtDNA), things can go very wrong.

Take cancer, for instance. Pitt's own Bennett Van Houten has studded mitochondria for decades. He and his partners think they may have unraveled one of cancer's more perplexing mysteries based on mitochondria's ability to make ATP (remember, ATP is like a battery for your cells). When mutations in mtDNA cause ATP production to go wild, cancer cells have access to an unlimited source of energy that they can use to grow and reproduce. Van Houten thinks that treatment targeting mitos could stop cancer in its tracks. But drugs that impact mitochondria in cancer cells will also hurt them in healthy cells. So the idea is to attack the cancer from two directions; target mitochondria with one medicine and use an effective chemotherapy drug to kill cancer cells. Initial testing in the lab looks promising, but it will be a while before scientists have this approach ready to use in patients.

Mitochondrial DNA may also be the key to new treatments for some neurological diseases. An exciting new development in Parkinson's disease research has shown that a certain mtDNA mutation creates a toxin that kills specific neurons in the brain - the ones that control voluntary movement. Over time, a Parkinson's patient can suffer from trembling, painfully stiff muscles, and can even lose muscular control. Sarah Berman, Pitt assistant professor of neurology, studies how mitochondria replicate in nerve cells. She noticed that if mitochondria don't fuse and divide properly in nerve cells, the cells die. She thinks that if we can find a way to ensure proper fusion and division, we might be able to stop Parkinson's before it starts. Turning that idea into reality is a long way off, but it shines a ray of hope into what has always been a dark diagnosis.

For more information on Parkinson's disease, please visit The Society for Neuroscience or the National Parkinson's Foundation. If you would like to know about the latests developments in cancer research and treatments try the American Cancer Society.