Dysfunction & Disease

Mitochondria are present in every tissue type of the human body and their role in energy production means that if the organelles are faulty, there can be catastrophic consequences. The fact that mitochondria are universally distributed means that diseases caused by their dysfunction cover a broad spectrum of classifications and subtypes. For this reason, faulty mitochondria often goes unnoticed as the source of a disorder.

There can be a number of reasons why mitochondria become faulty. Their mitochondrial genetic code may mutate randomly or as a result of a mutagen such as cigarette smoke. An individual could also inherit a mutated mitochondrial genome from their mother, such is the route of inheritance. The wrong genetic sequence would result in the incorrect coding of the important complexes involved in respiratory functions. The loss of energy production in mitochondria results in an "energy crisis" within that cell leading to cell dysfunction or death.

Diseases caused by mitochondrial dysfunction are usually present in areas of the body requiring the most metabloic activity, therefore mitochondrial disease is often present as neurological disorders (neurons are cells with high metabolism) which manifest as disorders of the muscular system known as myopathies. Unfortunately there are no cures for diseases caused by mitochondrial failure, diseases are merely managed.

Stethoscope image courtesy of wikimedia. This image is in the public domain and thus free of any copyright restrictions.

Mitochondrial disease can be broadly classified. Here are a few specific examples of diseases caused by mitochondrial dysfunction:

Leber's hereditary optic neuropathy (LHON) 

As the name suggests, this disease is characterised by the progressive loss of central vision in young people. Visual loss usually occurs in one eye first followed loss in the other after a pause of usually a month. Mitochondria dysfunction has been found in sufferers' retinal ganglion cells present in the optic nerve. The disease has a prevelence of 1:30,000 to 1:50,000 in Europe and is caused by a point mutation in the mitochondrial DNA (mtDNA).

Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)

This is a collection of predominantly neurological disorders affecting a range of functions and like LHON, NARP occurs in childhood or early adulthood. Sufferer's usually experience numbness, tingling or even pain in their arms and legs as well as muscle weakness and difficultly maintaining balance (ataxia). The disease also can progress to the light sensing cells of the retina causing visual loss (retinitis pigmentosa) or the disease may cause drooping of the eyelids (ptosis). In children, the disease can cause learning disabilities while in adults it may cause various forms of dementia. NARP is maternally inherited. The photo on the left shows how a sufferer of retinitis pigmentosa sees the world while the photo on the left shows a patient displaying ptosis.

Retinosa pigmentosa and ptosis images courtesy of wikimedia. These images are in the public domain and thus free of any copyright restrictions. 

Parkinson's disease

This well known neurodegenerative disorder affecting the central nervous system and results in the impairment of an individual's motor skills and speech. A sufferer's movements often slow (bradykinesia) as their muscles become rigid and a tremor is often present. Parkinson's disease is caused by the degeneration of the pigmented cells in the substantia nigra where the neurotransmitter dopamine is produced. Mitochondria have been found to be faulty in the pigmented cells of some sufferers of of Parkinson's disease and in this finding an interesting mechanism of disease induction comes to light. it was found that in order for cells to become faulty, a threshold of 60% of the mtDNA present must be mutated by a deletion. It is estimated that the prevalence of this disease is from 120-180 out of 100,000 among Caucasians while the prevalence in the African community is slightly lower.

Cancer

Mitochondrial dysfunction is believed to occasionally predispose cancer as well as contribute to its progression. It has been shown that sometimes normal cells which undergo a detrimental alteration in their respiratory machinery become malignant cancer cells. But another route may be down to the role of mitochondria in apoptosis (programmed cell death). It has been reported that apoptotic pathways are sensitive to different mitochondrial processes and so if mitochondria malfunction then apoptosis may not be regulated leading to cancer. Evidence for mitochondrial involvement in cancer has been produced when the mtDNA of 10 patients was with colorectal cancer was sequenced and mutations were found in 7 out of these 10 subjects.