Many diseases that people face are caused by mutations. Modern knowledge of genetic diseases is advancing, but it is still not always possible to determine what contributed to the mutation and what the consequences will be. Despite the increasing development of genetic engineering, treating the causes of genetic diseases is a challenge. Undoubtedly, a milestone in medicine will be the possibility of treating mitochondrial diseases.
What is a mitochondrion
Mitochondria are small cell organelles found in eukaryotic cells. Human body-building cells are classified as eukaryotic cells, i.e. cells that, among other things, have a cell nucleus. Mitochondria are responsible for cellular respiration processes. What does this mean in practice? These small organelles are responsible for the chemical conversion processes of the various compounds we provide with food, which need to be broken down into simple compounds that can be assimilated by the body. Mitochondria, as one of the few cellular organelles, have their own genetic material - DNA, which encodes the proteins necessary for the cell to function properly. Unfortunately, mitochondrial DNA can mutate, thereby disrupting its proper functioning. Mutations within the mit ochondrion can affect the so-called mitochondrial genome as well as the nuclear DNA.
Depending on which part of the DNA has mutated, this results in a variety of disorders in the normal functioning of the organelle. The largest concentrations of mitochondria are found in tissues with the highest energy requirements, such as nerve or muscle tissue, and therefore disruptions in the proper functioning of mitochondria are most often reflected in the functioning of the aforementioned tissues.
Inheritance of mitochondrial diseases
Interestingly, 'defective' mitochondrial genes are only passed on by the mother. Nevertheless, mitochondrial diseases can affect both boys and girls. Men who have a 'defective' copy of a gene found in mitochondrial DNA do not pass it on to their offspring. The researchers demonstrate that in families where a point mutation within the mitochondrial DNA has been identified in females, there is a high probability that female children will have this mutation. Importantly, in the case of genetic mutations within mitochondrial DNA, prenatal testing is not carried out for this.
Types of mitochondrial diseases
The subdivision of mitochondrial diseases is determined by where the mutation within the mitochondrial DNA occurred. On this basis, a distinction is made between diseases caused by mutations within the genomic mitochondrial DNA and mutations within the nuclear DNA. The following types of diseases with a mitochondrial basis are :
- NARP(neurogenic myopathy, ataxia,retinitis pigmentosa, NARP syndrome) - a disease caused by a point mutation within the mitochondrial genomic DNA. Point mutations mean that only one nucleotide building block of genomic DNA has been altered, but this results in the formation of a non-functional protein. The symptoms of the disease are mainly dementia, seizures, ataxia, sensory neuropathy, developmental delay, problems with brainstem development and function,
- CPEO(chronic progressive external ophtalmoplegia) - chronic progressive external ophthalmoplegia(muscle problem in the eyeball). The disease is caused by mutations involving deletion, or the removal of nucleotides within the genomic DNA,
- MNGIE (mitochondria neurogastrointestinal encephalomyopathy syndrome) - a chronic encephalomyopathy that affects the nervous system, stomach and intestines
- RBCsRRF(myoclonic epilepsy and ragged red fibres) - a disease caused by a point mutation of a nucleotide in mitochondrial DNA, the main symptoms of which areepilepsy, ataxia, myopathy, hearing loss and even optic nerve atrophy,
- RBCsLAS(mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) - the cause of RBCsLAS is a point mutation within the mitochondrial, genomic DNA. The main symptoms of the disease include lactic acidosis, stroke, seizures, problems with psychomotor activity, diabetes and short stature,
- LHON(Leber's hereditary optic neuropathy) - a disease that occurs primarily in boys, manifested by optic nerve atrophy, loss of vision, and encephalopathy,
- Pearson syndrome - is caused by a deletion, or loss of nucleotides in mitochondrial DNA. The main symptoms of Pearson's syndrome are anaemia, blood clotting disorders, problems with the normal functioning of the intestinal villi, liver dysfunction, sometimes hearing loss and mental retardation,
- Kerns-Sayre syndrome - symptoms of this syndrome are retinal pigmentary degeneration, ataxia, elevated protein levels in the cerebrospinal fluid.
Scientists speculate that specific mutations within mitochondrial DNA may contribute to conditions such as :
- breast cancer,
- ovarian cancer,
- thyroid cancer,
- leukaemia,
- alzheimer's disease,
- parkinson's disease,
- diabetes mellitus.
photo: panthermedia
Mitochondrial disease therapy
Unfortunately, modern medicine is still unable to cure mitochondrial diseases. In practice, palliative treatment is mainly used, consisting of the administration of pharmacological agents and surgery to help patients function. As patients suffer from energy deficits as a result of mitochondrial diseases, the administration of drugs and metabolites such as coenzyme Q10 or L-carnitine proves essential. The administration of antioxidant compounds such as vitamin E is also an important part of treatment.
What does the future hold? Researchers around the world are trying to develop novel therapeutic pathways to help people with mitochondrial diseases. At the moment, work is underway on the possibilities of modulating mitochondrial network dynamics, removing mitochondria that have mutated, and introducing normal genetic material into 'diseased' mitochondria. Hopefully, with scientific advances, an effective therapy to combat mitochodnrial diseases will soon be available.
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