(95)
12. Beskrive hvordan defekter i mitokondrielt DNA kan være årsag til (mindst en) sygdom
 Stryer, s.520-521
Devlin, s. 587-589

 

Mitochondria generate most of the ATP required by aerobic cells.

As befitting an organelle that is so central to energy  metabolism, mitochondrial malfunction can lead to pathological conditions. 

Mitochondrial diseases can appear as a result of: 

The accumulation of mutations in mitochondrial genes in the course of several decades may contribute to ageing, degenerative disorders and cancer (fx. Parkinson’s and Alzheimer’s)

 

Mitochondrial diseases are maternally inherited, because essentially all mitochondria present in a fertilized ovum are derived from the egg - several hundred thousand, while the sperm contributes only with few hundred mitochondria.  

Because the maternally inherited mitochondria are present in large numbers and not all mitochondria may be affected, the nature and severity of symptoms of the pathological condition may vary. As the percentage of defective mitochondria increases, energy-generating capacity diminishes until the cell can not function properly.

Organs that are highly dependent on oxidative phosphorilation, such as the nervous system and the heart, are most vulnerable to mutations in mtDNA. 

 

The first mitochondrial disease to be discovered was LHON - Leber hereditary optic neuropathy. It affects the CNS, including the optic nerves causing sudden-onset blindness in early adulthood due to death of the optic nerve.

The cause of this defect in many patients has been traced to a single base pair mutation in the mitochondrial DNA that changes an arginine to  histidine at amino acid 340 in NADH dehydorgenase subunit 4 of complex I in the inner mitochondrial membrane. Although it is not clear why this mutation leads to blindness, the eye requires a high level of mitochondrial activity and perhaps becomes sensitive over time to a small decrease in ATP synthesis by oxidative phosphorilation.

Other diseases due to mtDNA:

MELAS - mitochodnrial encephalopathy, lactis acidosis og stroke-like activity. As a result of a mutation in tRNA gene for leucine.

MERRF - myoclonic epilepsy and raged red fibers. Due to mutation in tRNA gen for lysine.

 

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