Mitochondrial diseases are a group of disorders relating to the mitochondria, the organelles that are the "powerhouses" of the eukaryotic cells that comprise higher-order lifeforms (including humans). The mitochondria convert the energy of food molecules into the ATP that powers most cell functions.

Mitochondrial diseases comprise those disorders that in one way or another affect the function of the mitochondria and/or are due to mitochondrial DNA.

Mitochondrial diseases take on unique characteristics both because of the way they are often inherited and because of the fact that mitochondria are so critical to cell function.

Mitochondrial inheritance behaves differently from the sort of inheritance that we are most familiar with. Regular nuclear DNA has two copies per cell (except for sperm and egg cells). One copy is inherited from the father and the other from the mother. Mitochondria, however, contain their own DNA, and contain typically from five to ten copies, all inherited from the mother. When mitochondria divide, the copies of DNA present are divided randomly between the two new mitochondria, and then those new mitochondria make more copies. As a result, if only a few of the DNA copies inherited from the mother are defective, mitochondrial division may cause most of the defective copies to end up in just one of the new mitochondria. Once more than half of the DNA copies are defective, mitochondrial disease begins to become apparent.

It should be noted, however, that not all of the enzymes and other components necessary for proper mitochondrial function are encoded in the mitochondrial DNA. A signficant portion of mitochondrial function is controlled by nuclear DNA instead. In addition, a few of the genes in mitochondrial DNA actually encode for enzymes that are used outside of the mitochondria.

To make things even more confusing, mutations to mitochondrial DNA occur frequently, due to the lack of the error checking capability that nuclear DNA has. This means that a mitochondrial disorder can occur spontaneously rather than be inherited. Further, sometimes the enzymes that control mitochondrial DNA duplication (and which are encoded for by genes in the nuclear DNA) are defective, causing mitochondrial DNA mutations to occur at a rapid rate.

The effects of mitochondrial disease can be quite varied. Since the distribution of defective DNA may vary from organ to organ within the body, the mutation that in one person may cause liver disease might in another person cause a brain disorder. In addition, the severity of the defect may be great or small. Some minor defects cause only "exercise intolerance", with no serious illness or disability. Other defects can more severely affect the operation of the mitochondria and can cause severe body-wide impacts.

However, even though mitochondrial disease varies greatly in presentation from person to person, several major categories of the disease have been defined, based on the most common symptoms and the particular mutations that tend to cause them:

  • Leber hereditary optic neuropathy (LHON)
  • Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS)
    • varying degrees of cognitive impairment and dementia
    • lactic acidosis
    • strokes
    • transient ischemic attacks
    • hearing loss
    • dysmotility
    • weight loss
  • Myoclonic epilepsy and ragged-red fibers (MERRF)
    • progressive myoclonic epilepsy
    • clumps of diseased mitochondria accumulate in the subsarcolemmal region of the muscle fiber and appear as "ragged-red fibers" when muscle is stained with modified Gomori trichrome stain
    • short stature
  • Leigh syndrome subacute sclerosing encephalopathy
    • after normal development the disease usually begins late in the first year of life, but the onset may occur in adulthood
    • a rapid decline in function occurs and is marked by seizures, altered states of consciousness, dementia, ventilatory failure
  • Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
    • progressive symptoms as described in the acronym
    • dementia
  • Kearn-Sayre syndrome (KSS)
    • external ophthalmoplegia
    • cardiac conduction defects
    • sensory-neural hearing loss
  • Myoneurogenic gastrointestinal encephalopathy (MNGIE)