Mitochondrial DNA Structure and Function

Mitochondria and Mitochondrial Disease

• Mitochondria have 37 genes, encoding 13 proteins, 22 transfer RNAs, and 2 ribosomal RNAs, essential for normal mitochondrial function.
• 13 mt genes encode proteins responsible for or involved in oxidative phosphorylation to create ATP for the cell's source of energy.
• Mitochondrial proteins are derived from both nDNA and mtDNA encoded genes.
• mtDNA is more prone to mutation than nDNA, leading to mitochondrial disease.

Characteristics of Mitochondrial Disease

• Mitochondrial disease refers to disorders caused by a reduction in ATP production.
• Symptoms include muscle weakness, problems with movement, diabetes, kidney failure, heart disease, dementia, loss of hearing, and abnormalities involving the eyes and vision.
• Visual component is often present, with features such as ptosis, external ophthalmoplegia, and retinitis pigmentosa.
• Leber's hereditary optic neuropathy is a result of mutations in four mitochondrial genes, affecting the enzyme complex I necessary for oxidative phosphorylation.

Inheritance of Mitochondrial Disease

• Mitochondrial disease is maternally inherited, as the mitochondria in the male sperm are lost during fertilization.
• Each cell has 1000s of copies of mtDNA, which are the same at birth (homoplasmy).
• Individuals with mutated mtDNA have a mixture of mutated and non-mutated mtDNA within a particular cell (heteroplasmy).
• The level of mutation in mtDNA affects the severity of disease in offspring, with high levels of mutation leading to severe disease.

Other Genetic Disorders

• Familial Hypercholesteremia is an autosomal dominant disorder due to a defect in the LDL receptor, leading to acceleration of atherosclerosis.
• Phenylketonuria is an autosomal recessive disorder due to a defect in the enzyme phenylalanine hydroxylase, leading to mental retardation if left untreated.
• Lysosomal storage disease is an autosomal recessive disorder resulting from a mutation in one of the genes encoding lysosomal hydrolases, leading to an accumulation of substrate within the lysosomes.
• Neurofibromatosis is an autosomal dominant disorder resulting from a defect in the neurofibromin 1 or 2 genes, leading to growths in the nervous system and skin.
• Haemophilia is an X-linked recessive disorder resulting from deficiencies in Factor VIII or IX, leading to impaired blood clotting and a risk of haemorrhaging.