Mitochondrial DNA: What are mitochondria?
Living things are made up of millions of tiny units of life called cells which are composed of extremely small functional parts called organelles. A mitochondrion is a cell organelle that has an extremely important role in the proper functioning of the cell. Also known as the ‘powerhouse of the cell’, mitochondria are responsible for producing chemical energy called ATP (adenosine triphosphate), which is necessary for all biological processes within the body to occur. Whilst energy production is the most important function of the mitochondria, scientists have placed too much importance on this function and relegated or neglected other important functions.
To be noted that the mitochondria also help in storing calcium, regulating metabolism, controlling cell death, and cell signalling, and carrying out various other functions.
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- Mitochondria have their own genome of about 16,500 bp that exists outside of the cell nucleus. Each contains 13 protein-coding genes, 22 tRNAs, and 2 rRNAs.
- They are present in large numbers in each cell, so fewer samples are required to construct an evolutionary tree.
- They have a higher rate of substitution (mutations where one nucleotide is replaced with another) than nuclear DNA making it easier to resolve differences between closely related individuals.
- They are inherited only from the mother, which allows tracing of a direct genetic line.
- They don’t recombine. The process of recombination in nuclear DNA (except the Y chromosome) mixes sections of DNA from the mother and the father creating a garbled genetic history.
What is Mitochondrial Inheritance?
Mitochondrial DNA is a special type of DNA and many people are not even aware this type of DNA actually exists. The human cell has two type of DNA: Nuclear DNA and Mitochondrial DNA. We even have 2 separate genomes – the nuclear DNA genome (which is linear in shape) and the Mitochondrial DNA genome (which is circular). Mitochondrial DNA is pretty basic in that it only contains 37 genes. Compared to nuclear DNA, which contains some 20,000 encoding genes, we can see that MtDNA has limited but important protein-coding functions. 13 of the 37 genes carried on MtDNA are involved in enzyme production.
What is also peculiar to MtDNA is the fact that this DNA is maternally inherited – males and females inherit a copy of MtDNA from their mother. Nuclear DNA, on the other hand, is inherited equally from both parents; a child will inherit 50% of their nuclear DNA from the mother and the other 50% from their father.
A MtDNA copy is passed down entirely unchanged, through the maternal line. Males cannot pass their MtDNA to their offspring although they inherit a copy of it from their mother.
This mode of inheritance is called Matrilineal or Mitochondrial Inheritance. There are a mitochondrial DNA testing services available which can help determine maternal lineage or whether the people tested share the same maternal line. Lineage DNA testing using MtDNA is ideal for testing ancient biogenetic origins and tracing one’s unique lineage. For instance, scientists have used MtDNA to compare the DNA of living humans of diverse origins to build evolutionary trees. MtDNA analyses suggest humans originated in Africa, appeared in one founding population some 170,000 years ago, then migrated to other parts of the world.
If there are any abnormalities in the mother’s mitochondria, they will be inherited by her offspring but if the father has abnormal mitochondria, he will not pass on the defect to his children since males do not pass on their MtDNA. Mitochondrial DNA plays such a pivotal role in providing the cell with energy that ineffective MtDNA functioning can lead to the cell malfunctioning or cellular death altogether. The areas that are mainly affected by MtDNA diseases include brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems.
Around 15% of mitochondrial diseases are due to a defect in the mitochondrial DNA itself. This defect can arise due to any number of external factors like exposure to harmful radiation, toxins, etc. or due to internal mix up by the cell. The majority of mitochondrial diseases are due to a defect in the nuclear DNA that controls the synthesis of mitochondrial proteins. A small but significant percentage of mitochondrial diseases are not inherited but acquired.
Since mitochondria are present in all types of cells, except red blood cells, a defect in one type of mitochondrial gene may produce an abnormality in the brain whereas, in another individual, it may produce a disease in the kidneys.
Since mitochondria are so widespread in the body and control incredibly diverse functions, the diseases of the mitochondria are just as diverse.
They most commonly cause neuromuscular diseases called mitochondrial myopathies that have typical symptoms of muscular weakness, loss of tone and restricted movement as well as sensory loss and loss of motor control.
- Leigh Syndrome: It presents with seizures, memory loss, and respiratory failure.
- Leber’s Hereditary Optic Neuropathy: There is a progressive loss of vision due to nerve damage. It leads to blindness in both eyes.
- Wolff-Parkinson-White Syndrome: It is a disease of the heart in which conduction defects occur.
- Diabetes and Deafness- This is a combination of both diabetes mellitus and deafness that occurs due to mitochondrial disease.
- Other diseases include abnormalities of the muscles in the gastrointestinal tract, limbs, heart, lungs, etc.
Overall, there is muscle weakness, poor growth, and visual and memory loss. Other organ systems may also be involved resulting in heart diseases, lung diseases, kidney diseases, disturbed bowel movements and liver problems, brain damage and hearing loss. Studies have also found links between certain cancers and MtDNA – they have linked the two via by-products known as reactive oxygen species (ROS) produced by MtDNA. Mitochondrial diseases are an intensive and diverse group of inherited or acquired defects that cause mild to severe organ damage and dysfunction resulting in a poor quality of life. They do not have a cure and are progressive, often leading to death.