Biological Energy, the Mitochondria, Disease & CoQ10
Many diseases are now being defined as "mitochondrial diseases"
Many diseases that previously lacked a definitive diagnosis are now understood to be mitochondrial diseases. While there is no formal definition of a “mitochondrial disease”, it is generally used today to describe genetic defects in the electron shuttling apparatus of the mitochondria. The electron transport system is responsible for charging the biological battery that drives energy synthesis. As it ultimately combines electrons with oxygen to make water, it is also commonly called the respiratory chain, referencing the oxygen consumption, or respiratory function. These diseases are frequently termed respiratory chain diseases.
The common denominator of mitochondrial respiratory chain disease is structural defects in one or more proteins that comprise the respiratory chain. This leads to impaired oxygen consumption and generation of energy. Patients with inherited genetic defects in the respiratory chain generally manifest increased fatigue, increased lactate, and central nervous system and/or muscle disturbances. Today- there are over 40 identified genetic defects associated with mitochondrial respiratory chain diseases that include both genetic errors in the mitochondrial genome and the nuclear genome. Despite advances in understanding the genetic basis of inherited mitochondrial diseases, the majority of patients who are clinically diagnosed with “mitochondrial disease” still do not carry a genetic diagnosis. By some estimates this population is placed at over 50%.
Defects in mitochondrial function primarily affect organs within the body that have high-energy demands including muscle and nervous tissue. For this reason mitochondrial diseases are also referred to as mitochondrial encephalomyopathies, connoting brain, skeletal and heart muscle involvement. The mechanism whereby a select mt(DNA) or n(DNA) defect gives rise to defined symptom complex and not others is a subject of considerable investigation, and is poorly understood. Notwithstanding this, respiratory chain diseases possess certain common biochemical features that include one or more of the following: 1) a reduction in oxygen consumption; 2) an increase in NADH; 3) an increase in lactate; 4) an increase in reactive oxygen species [ROS] (oxygen radicals); 5) a decrease in ATP production and 6) impairments in mitochondrial-mediated secondary messenger events associated with programmed cell death, inflammation, autophagy, and/or aging.
Defects in mitochondrial proteins leading to disease can arise through genetic errors in nuclear DNA (nDNA), mitochondrial DNA mt(DNA) or both. Listed above is a partial compilation of named mitochondrial diseases arising though mt(DNA) defects [adapted from DiMauro et. al.] The mitochondrial genome accounts for only a small fraction of the estimated 1200 gene products that comprise functioning mitochondrion. Analogous defects in n(DNA) can also give rise to mitochondrial disease. A partial list of n(DNA)-derived mitochondrial respiratory chain diseases include Friedreich’s ataxia, CoQ10 deficiency syndrome and Barth syndrome. Defects in the function of the respiratory chain have also been implicated in Huntington’s disease, Parkinson’s disease, metabolic syndrome, cancer, stroke and aging.