Mitochondrial DNA and Disease: Genes Outside the Nucleus

Structure of a mitochondrion
Structure of a mitochondrion | Source

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.

Structure of a cell; not all human cells have cilia or microvilli
Structure of a cell; not all human cells have cilia or microvilli | Source

Mitochondria and Mitochondrion

"Mitochondria" is a plural word. The singular form of the word is mitochondrion.

Unusual Organelles

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.

A diagram of a mitochondrion and a photo of a real one as viewed through an electron microscope
A diagram of a mitochondrion and a photo of a real one as viewed through an electron microscope | Source

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 a few alterations produced by 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

The majority of a cell's DNA is located in the nucleus. DNA is combined with a small amount of protein to make chromosomes.
The majority of a cell's DNA is located in the nucleus. DNA is combined with a small amount of protein to make chromosomes. | Source

Mitochondrial 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.

This is a map of all the genes in a mitochondrial DNA molecule. The genes are represented by capital letters.
This is a map of all the genes in a mitochondrial DNA molecule. The genes are represented by capital letters. | Source

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.

Mutations

A DNA molecule contains 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.

This is a flattened section of a DNA molecule. The molecule has the shape of a double helix and is made of two strands. Only one strand is "read" when the instructions in the genetic code are being followed.
This is a flattened section of a DNA molecule. The molecule has the shape of a double helix and is made of two strands. Only one strand is "read" when the instructions in the genetic code are being followed. | Source

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.

Genetic Counselling

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

Consultation with a Physician

Anyone with symptoms that may indicate the presence of a mitochondrial disease should consult a doctor for a diagnosis and treatment recommendations.

Possible Symptoms

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
  • diabetes
  • dementia

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

Frequency of Disease

It's thought that about one in four thousand people in the United States have a mitochondrial disease.

Possible Treatments

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.

Ongoing research into the structure and function of DNA may help people suffering from a mitochondrial disease.
Ongoing research into the structure and function of DNA may help people suffering from a mitochondrial disease. | Source

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.

© 2012 Linda Crampton

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Comments 10 comments

reviewblog 4 years ago

thannks for this info i never knew Mitochondrial can occur and the uteria of the sickness


AliciaC profile image

AliciaC 4 years ago from British Columbia, Canada Author

Thank you for the comment, reviewblog. Mitochondrial disease has suffered from a lack of publicity in the past, but organizations and individuals are working hard to change this. Many more people may be suffering from a mitochondrial problem than those who are currently diagnosed.


shara63 profile image

shara63 4 years ago from Delhi

wonderful information...i wish more new discoveries in this direction are made and facilitate the sufferers to resolve their mitochondrial problems very soon!


AliciaC profile image

AliciaC 4 years ago from British Columbia, Canada Author

Thanks for the visit and the comment, shara63. I hope very much that new discoveries are made very soon, too. Some people have a horrible experience with mitochondrial disease.


Seeker7 profile image

Seeker7 4 years ago from Fife, Scotland

This is awesome and fascinating - I wish I had better adjectives to described this wonderful hub. I had no idea that you could have DNA that was circular? I find this mind blowing!! As a nurse you learn a little about the cell and it's workings, but I think your hub just highlights how badly our learning on this subject falls short.

I listenend with great interest to the physician who had to go through such a horrible 6 years until she was given a proper diagnosis. It really angers me how many people are fobbed of, basically because many of the those practising medicine haven't a clue. It's the classic case of - if it isn't written down in some dam science book they read at uni., then it doesn't exist - the patient just has to be nuts or imagining it etc. I'm glad she kept pushing and hopefully it will give many others the courage to keep going as well until the get the proper diagnosis that will hopefully, help them to get their lives back.

This was voted up everything, except funny + shared. I loved this awesome hub!!


AliciaC profile image

AliciaC 4 years ago from British Columbia, Canada Author

Thank you so much for the wonderful comment, the votes and the share, Seeker7!!! I appreciate them all very much. I enjoyed writing this hub and doing research for it, as I always do, but this time the research touched me deeply. Some of the videos of serious mitochondrial disease sufferers on You Tube - especially of the children - are heartrending. Our mitochondria are such a major part of our existence and could be involved in far more illnesses that we realize. I think that research into mitochondrial diseases should be given a much higher priority.


kashmir56 profile image

kashmir56 4 years ago from Massachusetts

Hi my friend, WOW this is all great and interesting information in this well written hub that i did not know before. Thanks so much for helping me understand and learn more about this .

Vote up and more !!!


AliciaC profile image

AliciaC 4 years ago from British Columbia, Canada Author

Hi, Tom. I appreciate the comment and the vote! Thank you for the visit.


drbj profile image

drbj 4 years ago from south Florida

It is not easy nor simple, Alicia, to write an explanatory hub that is not only easy to read but rife with so much information. Brava, you have done just that with the subject of mitochondrial DNA and allied disorders.


AliciaC profile image

AliciaC 4 years ago from British Columbia, Canada Author

Thank you, drbj. I appreciate your kind comments so much!

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