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Mitochondrial DNA and Disease: Genes Outside the Nucleus
What Are Mitochondria?
Mitochondria are organelles that have a vital function in our lives. They produce the majority of the energy that our cells need in order to function. Since our body is made of cells, without mitochondria we couldn’t survive. The energy that the mitochondria produce is temporarily stored in ATP (adenosine triphosphate) molecules. These travel to wherever they are needed and release energy as required.
Mitochondria have another important characteristic. In human and animal cells, they’re the only location of DNA outside the nucleus. An error in mitochondrial DNA or in the nuclear DNA that controls the mitochondria may have serious consequences in our bodies. The damage can stop the organelles from working properly and cause hundreds of different disorders. These disorders are collectively known as mitochondrial diseases.
"Mitochondria" is a plural word. The singular form of the word is mitochondrion.
Mitochondria are unusual organelles. Not only do they contain DNA molecules, but the molecules are circular. Humans, other animals, and plants have linear DNA. Another unusual feature of mitochondria is that they can reproduce independently of the cell that contains them. A human cell may contain hundreds or even thousands of mitochondria.
Bacteria have circular DNA. A popular scientific theory says that millions of year ago mitochondria were independent, bacteria-like organisms. At some point in time, the organisms were engulfed by a larger cell. Instead of being destroyed, the trapped organisms survived and became a permanent part of their host. They received nutrients from the host cell and in turn made ATP molecules that the host used. This type of relationship is called endosymbiosis—a situation in which two organisms live together and interact with each other, with one organism living inside the other.
DNA and Genes
DNA is the abbreviation for deoxyribonucleic acid. The forty-six DNA molecules in the nucleus of our cells are combined with protein to make structures called chromosomes. The deoxyribonucleic acid in the chromosomes contains encoded instructions for making our body and controlling how it works. (Additional factors influence these functions.) The code "tells" a cell to make specific proteins needed for life. A gene is a section of a DNA molecule that codes for one particular protein.
The nucleus of every cell in our bodies contains the same genetic instructions, with the exception of differences due to mutated genes. Egg and sperm cells are another exception, since they contain only twenty-three chromosomes. Different genes are active in different parts of the body.
DNA can’t leave the nucleus, so it requires help in the process of making proteins. A molecule called RNA or ribonucleic acid is made from the genetic code. The RNA transports the instructions from the DNA to the ribosomes outside the nucleus. Here the proteins are produced.
The Nucleus, Chromosomes, and DNA
Mitochondrial DNA is also known as mtDNA. There are two to fifteen mtDNA molecules in each mitochondrion. Each molecule contains thirty-seven genes, which are all involved in controlling mitochondrial processes and chemical manufacture within the organelle.
The DNA molecules in the nucleus contain about 20,000 to 25,000 genes. About 1500 of these genes control the function of the mitochondria. According to one theory, the genes migrated to the nucleus from the organisms that became mitochondria.
Mutations (changes) in mitochondrial DNA or in the nuclear genes that affect the mitochondia can result in a mitochondrial disease. A huge number of biological processes and chemical reactions are constantly occurring in our cells and in the tissues and organs that they form. Many of these processes require energy, so malfunctioning mitochondria can have serious and widespread effects in our bodies. Some ATP molecules can be made outside the mitochondria, but not enough are produced in this location to keep us alive.
Inheritance of Mitochondria and Mutated Genes
A person's mitochondria are inherited from his or her mother. During fertilization, the sperm penetrates the egg. The genetic material of the egg and sperm join, but the rest of the sperm—including its mitochondria —disintegrates. The egg contains the mitochondria that the baby will inherit.
Once the process of fertilization has finished, the egg is known as a zygote. This is the first cell of the new individual. If the egg's mitochondria contained mutated DNA, the zygote's will as well.
The zygote contains genetic material from both the mother and the father. If the genes controlling the mitochondria are mutated in either of these sources, the zygote will inherit them.
A DNA molecule contains four nitrogenous bases named adenine, thymine, cytosine, and guanine. The molecule is double-stranded. The bases occur repeatedly throughout each strand. The order of bases in one strand forms the genetic code. A change in the order of bases, or a mutation, means that the genetic code has changed.
Inheritance of a Mitochondrial Disease
Unfortunately, although it's sometimes possible to predict the probabilty that a child will inherit mutated genes related to mitochondrial disease, it's not always possible to predict the effect of this inheritance. There are many variables involved.
Mitochondrial Gene Mutations
If the mitochondria in the zygote contain a mutation, the child that develops may experience no symptoms, mild symptoms, or serious ones. If only some of the mitochondria in a zygote contain a mutation, the child will contain a mixture of normal and mutated organelles. This may affect the symptoms that he or she experiences.
The nature of the mutations and the parts of the body where mitochondria with specific mutations are located will also affect the symptoms. When a cell divides to make new cells during the production of a baby, a selection of mitochondria go to each daughter cell instead of a complete set. The distribution of the mitochondria appears to be random. This means that we can't predict where specific versions of the organelles will end up.
Nuclear Gene Mutations
When parents have mutations in the nuclear genes controlling the mitochondria, the effects on the offspring are variable. They depend on the nature of the mutations and on whether one or both parents have a mutation. A child may be ill, healthy but a carrier of a gene for mitochondrial disease, or healthy and not a carrier.
Prospective parents who have a mitochondrial disease or who are carriers of a mutated gene may need help when considering whether their children will have problems. A genetic counsellor can provide information about inheritance and symptom possibilities and probabilities.
A Patient Describes Her Experience
Primary and Secondary Disease
An inherited mitochondrial problem is present at birth and is known as a primary condition. If this problem produces symptoms, they may appear immediately after birth. They may not appear until later, however. They may even be delayed until adulthood, as they were for the patient in the video above.
Mitochondrial dysfunction may develop during a person's lifetime without the presence of a relevant mutation. This condition is known as secondary mitochondrial disease. One cause of the condition is exposure to toxins that enter the body from the outside or are made inside the body. If the toxins damage the mitochondria, organelle dysfunction may develop. The condition may also arise after a serious health problem such as a heart attack or as a result of the aging process.
Living With Mitochondrial Disease
Anyone with symptoms that may indicate the presence of a mitochondrial disease should consult a doctor for a diagnosis and treatment recommendations.
The following symptoms are not unique to mitochondrial disease but may also appear due to other illnesses. It's more likely that a mitochondrial disorder is responsible for the symptoms if they involve several organ systems.
Effects of the disease may include:
- vision or hearing problems
- learning and developmental problems
- heart, kidney or liver problems
- gastrointestinal problems
- respiratory problems
- neurological problems and seizures
- thyroid problems
- poor growth
A combination of medical tests are necessary before a doctor will diagnose a mitochondrial disease. These tests are often performed or ordered by a specialist and usually involve a muscle biopsy.
A Doctor Discusses Diagnosis and Treatment
It's thought that about one in four thousand people in the United States have a mitochondrial disease.
Many mitochondrial diseases have been described and named, but researchers say that there are almost certainly many additional ones that haven't yet been discovered. There is growing evidence that mitochondrial malfunction is not a rare disorder and is involved in some diseases of aging and perhaps even in the aging process itself.
At the present time, mitochondrial diseases can't be cured. They can often be helped by treating the symptoms, however. For example, anticonvulsant medications can help seizures and physical therapy can help movement problems. Parenteral nutrition (a process in which nutrients are provided intravenously) can replace conventional ingestion and digestion, which require energy. Dietary therapy may be helpful, depending on the specific version of the disease that is diagnosed. Specific supplements may be useful for some patients.
It's important for a person with a mitochondrial disease to get enough rest. Avoiding physiological stress that requires energy to remove, such as exposure to very high or very low temperatures, infections, and toxins, is also very important.
The Importance of Further Research
At the moment, mitochondrial disease is frustrating for patients, their families, and their doctors. It's a complex, poorly understood condition that's hard to recognize and hard to treat. However, the good news is that researchers are becoming more aware of the significance of the disease. Hopefully the rate of new discoveries will increase and we will soon have better ways to help people with problems caused by malfunctioning mitochondria.
"What Are Mitochondria?" Mitochondrial Biology Unit, University of Cambridge. http://www.mrc-mbu.cam.ac.uk/what-are-mitochondria (accessed August 18, 2017).
"Mitochondrial DNA." U.S. National Library of Medicine. https://ghr.nlm.nih.gov/mitochondrial-dna (accessed August 18, 2017).
"About Mitochondrial Disease - Mito FAQ" Mitoaction. http://www.mitoaction.org/mito-faq (accessed August 18, 2017).
© 2012 Linda Crampton