Mitochondria Cellular Power Plants For the Body
By Dr. Richard Newman // December 12, 2013
mitochondria have their own DNA
ABOVE VIDEO: A general overview of Mitochondrial disorders.
It takes energy to run all the processes in all of our bodies’ cells. The fuel for this energy, in the form of sugar and fat, comes from the food we eat.
After the fuel is digested, it is delivered to and enters the cells. It is in turn delivered to cellular organelles called mitochondria, in which it is processed in a sequence of steps referred to as cellular respiration and turned into the energy storage compound ATP.
The ATP supplies energy to all of the metabolic and enzymatic reactions required for cellular life to continue. A great deal of ATP is needed. In fact, calculations suggest that every day approximately 47 pounds of ATP must be produced, utilized, and recycled for an average adult. The mitochondria must be in good working order to accomplish this monumental feat.
Once the breakdown products of sugar and fat enter the mitochondria, energetic electrons are transferred via a chain of five respiratory “complexes,” which are large multi-unit proteins. Complex I, in fact, is one of the largest human proteins, with 45 protein subunits, each encoded by a unique gene.
The mitochondria are so complex that an estimated 20 percent of the estimated 180,000-200,000 genes in the human genome are involved in mitochondrial structure, function, and production. Any breakdown in the process can therefore interfere with energy production and cause a breakdown in cellular function.
The mitochondria have their own DNA, separate from the 23 chromosome pairs inside the cell’s nucleus. The mitochondrial chromosome, however, only encodes 13 specific genes.
The mitochondria are so complex that an estimated 20 percent of the estimated 180,000-200,000 genes in the human genome are involved in mitochondrial structure, function, and production. Any breakdown in the process can therefore interfere with energy production and cause a breakdown in cellular function.
The process can fail in the face of two major types of problems. Genetic mutations may cause some component of Complex I to function suboptimally or fail completely, and toxic damage to one of the components.
Mitochondrial Mutations Underlie Many Conditions
A mutation can be “major” and cause problems at a young age. These can include poor growth, muscle weakness, uncoordination, vision and hearing loss, developmental delay, mental retardation, heart, liver, kidney, and gastrointestinal disorders, diabetes and seizures.
They can occasionally be fatal in children in severe form. Mitochondrial dysfunction is said to underlie the largest percentage group of identifiable causes of autism (which can coexist with other systemic problems including muscle disease).
In adults, less severe mutations may play a role in such problems as dementia, early aging, and muscle disease. Mitochondrial dysfunction is identifiable in Alzheimer’s disease and in Parkinson’s disease (PD). There are now mutations identified in approximately 13 different genes in familial PD, some of which affect mitochondrial function.
Environmental toxins including DDT and rotenone (banned pesticides) and dioxin (Agent Orange) are known to damage the mitochondrial complex, and exposures have been linked to PD. Medications may interfere with mitochondrial function.
Muscle pain and weakness (and less commonly memory and cognitive issues are encountered as a side effect of cholesterol-lowering agents (“statin myopathy”). Valproic acid, used for treatment of epilepsy, migraines, and bipolar illness, interferes with the utilization of fat compounds in mitochondria, and may thus cause problems with liver function as well as fetal nervous system malformations and autism.
Mitochondrial Dysfunction Presents Diagnostic Challenge
Many mitochondrial diseases go unrecognized, especially in adults. They should be considered in patients who have symptoms related to more than one organ system (e.g. muscle and brain). Additionally in a multicenter study of several hundred patients with diagnoses of fibromyalgia, 40 percent were shown to have a mitochondrial muscle disease.
A common presentation in my office is a patient with chronic and progressive fatigue, burning muscle pain (possibly from lactic acid buildup in cells trying to manufacture ATP via an alternative pathway), cognitive problems, digestive issues (constipation, gastroparesis), and sometimes autonomic disorders.
I became interested in such problems many years ago when a complicated patient with a known diagnosis challenged me to learn more about her problem (which also affects her two sons).
Since then I have confirmed such diagnoses in about 50 patients, whose diagnoses had previously eluded their physicians. The evaluation typically involves three phases. The patient’s history and examination will yield important clues to suggest mitochondrial disease.
A complex set of screening blood and urine tests are performed. These are to look for indicators of metabolic abnormalities, and also some conditions, which can mimic mitochondrial diseases but are of different origins (e.g. autoimmune muscle disorders).
If the findings are indeed suspicious, many patients will require a muscle biopsy for special metabolic studies and to view any structural pathology in muscle tissue.
Although specific treatment of such disorders is difficult, the identification of a clear diagnosis in many patients may become a reward in itself. There are also excellent support organizations for patients and families, including the United Mitochondrial Disease Foundation (umdf.org) and MitoAction (mitoaction.org).
I am pleased to assist in the evaluation and treatment of patients with these complex disorders at First Choice Medical Group.
ABOUTH THE AUTHOR
With over 25 years’ experience in Neurology, Dr. Richard Newman is Fellowship trained by the National Institute of Health in Movement Disorders.
A graduate of SUNY, Buffalo School of Medicine in New York, Dr. Newman completed his internship in Internal Medicine at Millard Fillmore Hospital in Buffalo, New York.
He is a Diplomate of the American Board of Psychiatry and Neurology, a Fellow of the American Academy of Neurology, and a member of the American Medical Association and Florida Medical Association.
Dr. Newman specializes in the treatment of balance and movement challenges relating to metabolic muscle and brain disorders, spine disorders and injuries, Tourette Syndrome, Alzheimer’s Disease, Lou Gehrig’s Disease, Dystonia and Parkinson’s Disease, among others; stroke management; vertigo; autism and Attention Deficit Disorder.
