Inherited and acquired mitochondrial DNA damage causes a diverse range of symptoms and illnesses depending upon the organs that are affected:
The symptoms of mitochondrial diseases affect the cells of the brain, nerves, muscles, kidneys, heart, liver, eyes, ears and pancreas. In some patients, only one organ is affected, while in other patients all the organs are involved. In both inherited and acquired mitochondrial DNA damage tissues with high demands for energy, such as muscle, heart, brain and eye are more vulnerable to mitochondrial defects. Depending on how severe the mitochondrial disorder is, the illness can range in severity from mild to fatal.
Mitochondrial disorders with neurological manifestations include; ophthalmoplegia, exercise intolerance, fatigability, myopathy, ataxia, seizures, myoclonus, stroke, optic neuropathy, peripheral neuropathy, glaucoma, dementias, deafness, peripheral neuropathy, headache, dystonia, myelopathy, Parkinson’s disease, Multiple System Atrophy (MSA), Alzheimer’s disease and Lou Gehrig’s disease.
Mitochondrial disorders with systemic manifestations include; atherosclerotic heart disease, cardiomyopathy, cardiac conduction defects, diabetes, short stature, cataract, pigmentary retinopathy, metabolic acidosis, hepatopathy, nephropathy, intestinal pseudo-obstruction, pancytopenia, Alzheimer’s, Parkinson’s, Lou Gehrig’s, peripheral neuroapthy, glaucoma, sideroblastic anemia, exocrine pancreatic dysfunction and hypoparathyroidism.
The most prevalent mitochondrial diseases are degenerative diseases of aging resulting from acquired mitochondrial DNA damage and depletion of healthy mitochondria. The deletions of mitochondrial DNAs that are present in massive amounts in rare inherited diseases like Kearns-Sayre and Pearson syndromes are also present in much smaller amounts in the normal elderly; such deletions increase progressively in long-lived tissues, such as muscle and brain. Many symptoms of mitochondrial diseases, such as muscle weakness, diabetes, vision loss, hearing loss, and dementia, are also the hallmarks of aging. Mutated mitochondrial DNAs have roles in the progressive symptoms of late-onset Neurodegeneration, such as Parkinson's and Alzheimer's diseases. The mitochondrial theory of aging, proposed many years ago, now has experimental support.
Mitochondrial DNA mutates up to twenty times as rapidly as nuclear DNA, because mitochondria lack an efficient DNA repair system which would recognize and replace damaged bases when DNA is copied, as happens with Nuclear DNA. Depletion of mitochondrial DNA occurs progressively during the preclinical and clinical stages of diseases of aging and to some extent during ‘normal’ aging.
Mitochondrial DNA mutates considerably during the growth and metastases of breast, colon, kidney, liver, leukemia, lymphoma and stomach tumors and control of this excessive mutation may provide therapeutic potential.