Cancer:
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| mtDNA Mutation |
Cancer:
Mitochondrial DNA is prone to somatic mutations, which are a type of non-inherited mutation. Somatic mutations occur in the DNA of certain cells during a person's lifetime and typically are not passed to future generations. There is limited evidence linking somatic mutations in mtDNA with certain cancer types, including breast, colon, stomach, liver and kidney tumors. These mutations might also be associated with cancer of blood-forming tissue (leukemia) and cancer of immune system cells (lymphoma).
It is possible that somatic mutations in mtDNA increase the production of potentially harmful molecules called reactive oxygen species. MtDNA is particularly vulnerable to the effect of these molecules and has a limited ability to repair itself. As a result, reactive oxygen species easily damages mtDNA, causing a buildup of additional somatic mutations. Researchers are investigating how these mutations could be related to uncontrolled cell division and growth of cancerous tumours.
Cyclic Vomiting Syndrome:
Cyclic vomiting syndrome may be related to genetic changes in mitochondrial DNA. Some of these changes alter single DNA building blocks (nucleotides), whereas others rearrange larger segments of mitochondrial DNA. These changes likely impair the ability of mitochondria to produce energy. Defects in energy production may lead to symptoms during periods when the body requires more energy, such as when the immune system is fighting an infection. However, it remains unclear how changes in mitochondrial function are related to recurrent episodes of nausea and vomiting
Kearns-Sayre syndrome:
Most people with Kearns-Sayre syndrome have a single, large deletion of mitochondrial DNA. The deletions range from 1,000 to 10,000 nucleotides, and the most common deletion is 4,997 nucleotides. Kearns-Sayre syndrome primarily affects the eyes, causing weakness of the eye muscles (ophthalmoplegia) and breakdown of the light-sensing tissue at the back of the eye (retinopathy). The mitochondrial DNA deletions result in the loss of genes that produce proteins required for oxidative phosphorylation, causing a decrease in cellular energy production. Researchers have not determined how these deletions lead to the specific signs and symptoms of Kearns-Sayre syndrome, although the features of the condition are probably related to a lack of cellular energy. It has been suggested that eyes are commonly affected by mitochondrial defects because they are especially dependent on mitochondria for energy.
Leigh syndrome Mutations in one of several different mitochondrial genes can cause Leigh syndrome, which is a progressive brain disorder that usually appears in infancy or early childhood. Affected children may experience delayed development, muscle weakness, problems with movement, or difficulty breathing.
Some of the genes associated with Leigh syndrome provide instructions for making proteins that are part of the large enzyme complexes necessary for oxidative phosphorylation. For example, the most commonly mutated mitochondrial gene in Leigh syndrome, MT-ATP6, provides instructions for a protein that makes up one part of complex V, an important enzyme in oxidative phosphorylation that generates the majority of the cell's energy (ATP) in the mitochondria. The other genes provide instructions for making transfer RNA molecules, which are essential for protein production within mitochondria. Many of these proteins play an important role in oxidative phosphorylation. The mitochondrial gene mutations that cause Leigh syndrome impair oxidative phosphorylation. Although the mechanism is unclear, it is thought that impaired oxidative phosphorylation can lead to cell death in sensitive tissues, which may cause the signs and symptoms of Leigh syndrome.
More on mtDNA Mutation Disorders: http://ghr.nlm.nih.gov/chromosome/MT
Kearns-Sayre syndrome:
Most people with Kearns-Sayre syndrome have a single, large deletion of mitochondrial DNA. The deletions range from 1,000 to 10,000 nucleotides, and the most common deletion is 4,997 nucleotides. Kearns-Sayre syndrome primarily affects the eyes, causing weakness of the eye muscles (ophthalmoplegia) and breakdown of the light-sensing tissue at the back of the eye (retinopathy). The mitochondrial DNA deletions result in the loss of genes that produce proteins required for oxidative phosphorylation, causing a decrease in cellular energy production. Researchers have not determined how these deletions lead to the specific signs and symptoms of Kearns-Sayre syndrome, although the features of the condition are probably related to a lack of cellular energy. It has been suggested that eyes are commonly affected by mitochondrial defects because they are especially dependent on mitochondria for energy.
Leigh syndrome Mutations in one of several different mitochondrial genes can cause Leigh syndrome, which is a progressive brain disorder that usually appears in infancy or early childhood. Affected children may experience delayed development, muscle weakness, problems with movement, or difficulty breathing.
Some of the genes associated with Leigh syndrome provide instructions for making proteins that are part of the large enzyme complexes necessary for oxidative phosphorylation. For example, the most commonly mutated mitochondrial gene in Leigh syndrome, MT-ATP6, provides instructions for a protein that makes up one part of complex V, an important enzyme in oxidative phosphorylation that generates the majority of the cell's energy (ATP) in the mitochondria. The other genes provide instructions for making transfer RNA molecules, which are essential for protein production within mitochondria. Many of these proteins play an important role in oxidative phosphorylation. The mitochondrial gene mutations that cause Leigh syndrome impair oxidative phosphorylation. Although the mechanism is unclear, it is thought that impaired oxidative phosphorylation can lead to cell death in sensitive tissues, which may cause the signs and symptoms of Leigh syndrome.
More on mtDNA Mutation Disorders: http://ghr.nlm.nih.gov/chromosome/MT
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