Mitochondrial Oxidative Decay and Eye Disease
June 16, 2006
Mitochondria are the most complex organelles in the cell; they provide energy for all basic metabolic processes including those associated with the retina. They detoxify oxygen, function in calcium and iron homeostasis, and they play a key role in programmed cell death. Oxygen (free radical) damage is produced as an inevitable byproduct of mitochondria function. Mitochondria are particularly vulnerable to this damage as they contain their own DNA.
A review published in the August 2005 Molecular Aspects of Medicine, on over 130 biochemistry, molecular biology and nutrition peer-reviewed journal articles, suggests that optimal metabolic function of mitochondria depends on the availability of many essential minerals, vitamins and other metabolites. Unfortunately, micronutrient deficiencies are widespread in the U.S. population and these deficiencies are associated with most degenerative disease processes. The mitochondria micronutrients specifically include:
"Iron" Normal aging of the brain and neurodegenerative changes share certain pathological and physiological changes with the retina, including mitochondrial dysfunction, oxidative stress, and loss of iron homeostasis, which naturally declines with age. It is becoming clear that many organs show morphologic, physiologic, and biochemical changes before hemoglobin levels change. Heme, the major intracellular functional form of iron, is synthesized in the mitochondria and the decline in synthesis could explain the loss of iron homeostasis in aging.
"Zinc" Low zinc intakes are common, as 10% of the US population ingest under 50% of the RDA. Zinc deficiency in human cells in culture causes marked release of oxidants resulting in significant oxidative damage to DNA. Zinc deficiency is also associated with cancer.
"Copper "A link between copper and iron metabolism is well established. Copper deficiency increases dietary iron absorption, which is probably a compensatory mechanism to increase mitochondria heme production.
major component of the mitochondrial antioxidant defense system is
manganese-dependent super oxide dismutase (MnSOD). Inadequate manganese
levels increase mitochondrial oxidants and subsequent mitochondrial
decay. Low levels of manganese can be associated with impaired glucose
tolerance, as well as altered carbohydrate and lipid metabolism.
"Selenium" Several reports have shown selenium deficiency causes defects in mitochondrial structure, integrity, and electron transport chain function. Dietary selenium deficiency occurs in areas of the world where selenium is deficient in the soil. An increased risk of cancer and decreased immune system function has been associated with selenium deficiency.
"Magnesium" The mitochondria accounts for nearly one third of total cellular magnesium. Magnesium is required for mitochondria ATP energy. Moderate magnesium deficiency is common, particularly among African-Americans and is associated with increased risk for hypertension and diabetes.
"Calcium" Calcium is sequestered in mitochondria and it participates in cellular calcium signaling. Calcium is also a required cofactor in several mitochondrial proteins, including dehydrogenates (enzymes that take up hydrogen).
"Vitamin B6" Vitamin B6 is converted to pryidoxal-5 phosphate, which is directly involved in mitochondrial heme biosynthesis. Approximately 10% of the US population consumes less than half of the B6 RDA. Recent epidemiological studies have indicated an association between B6 deficiency and increased cancer.
"Vitamin B12" Vitamin B12 is taken into the mitochondria and plays an important role in amino acid metabolism. A B12 deficiency has been shown to affect 10-15% of individuals over the age of 60 in the U.S. Patients with B12 deficiency exhibit megaloblastic anemia and often hyperhomocysteinemia, which has been associated with increasing the risk of dry AMD progressing to wet AMD.
"Biotin" Biotin deficiency is suggested to deplete the amino acid, glycine, from the mitochondrial matrix. Glycine depletion results in heme deficiency.
"Panthothenic Acid" Also knows as Vitamin B5, is the precursor of coenzyme A (CoA), which is necessary for mitochondrial ATP energy production.
"Lipoic Acid" Lipoic acid is both water and fat soluble and is a vital cofactor for production of enzymes necessary for mitochondrial function. Both lipoic acid and B5 are essential for the normal supply of succinyl-CoA, another precursor for heme biosyntheses.
"Riboflavin" Also known as Vitamin B2, supports mitochondrial energy production by stimulating metabolism of fats, carbohydrates, and proteins. It is required for red blood cell formation and respiration, antibody production, growth and reproduction. It also helps in the prevention of many types of eye disorders, including bloodshot, itching or burning eyes and abnormal sensitivity to light.
"Acetyl-L-Carnitine"- ALC is a delivery form for the amino acid, L-carnitine. It transports Omega-3 long-chain fatty acids across the mitochondrial membranes into the mitochondria and transports small-chain and medium-chain fatty acids out of the mitochondria in order to maintain normal coenzyme A levels in these organelles. This is particularly important for maintaince of retina health.
"Coenzyme Q10"- CoQ10 is a fat-soluble compound primarily synthesized by the body and also consumed in the diet. It is required for mitochondrial ATP synthesis. It also functions as an antioxidant in cell membranes and lipoproteins. Statin drugs deplete CoQ10 levels, therefore CoQ10 supplements should be routinely taken with all statin drugs.
Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging. Ames Bruce, Atamna Hani, Killilea David, Molecular Aspects of Medicine. 2005 Aug-Oct;26(4-5):363-78 [ abstract]