Involvement of mitochondria in apoptosis, neurodegeneration and ageing

Ageing Mitochondria are components of our cells that generate the majority of our energy from nutrients. Mitochondria however, have a dark side. Through their normal activity, they generate unstable chemicals that harm both the mitochondrion itself and other components of the cell. These unstable chemicals are reactive oxygen species and mtDNA has a relatively high chance of getting damaged by these chemicals. This resulting damage is thought to play a important role in ageing. Techniques are currently developed trying to reverse the damage being made by mitochondria. If mitochondria play such crucial roles in ageing, then these discoveries could possibly lead to the first anti-ageing therapy. Neurodegeneration Some neurodegenerative disorders are also a result of mitochondrial dysfunction. Examples are Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and amyotropic lateral sclerosis. Mitochondrial DNA from Alzheimer’s and Parkinson’s patients and mitochondrial activity in amyotropic lateral Sclerosis patients is altered. It is thus important to explore the possibility that mitochondrial dysfunction may be an important factor in the late onset and progression of neurodegenerative disease. Apoptosis Thirdly, mitochondria play an important role in the regulation of cell death. They contain many pro-apoptotic proteins such as cytochrome C. Mitochondrial shape however, also plays an important role in the event of apoptosis. Mitochondria are able to fuse and split from/with each other. Several studies indicate that mitofusins and optic atrophy 1 (Opa1) are essential for mitochondrial fusion, whereas fission 1 (Fis1) and dynamin-related protein 1 (Drp1) are essential for mitochondrial fission. Disruption of mitochondrial fission and fusion has been linked to the development and progression of some diseases. When cells are exposed to high stress, mitochondria undergo fission and will eventually commit suicide by means of apoptosis. Under low levels of stress however, mitochondria undergo fusion instead of fission. This process is called Stress-induced mitochondrial hyperfusion. In this Stress-induced mitochondrial hyperfusion pathway, three differences in protein requirements were found. Mitophagy, a process where mitochondria are engulfed by autophagosomes, is also under influence of stress. Outline of thesis Understanding the dynamics in mitochondria is important because these dynamics regulate mitochondrial behavior concerning cell death. The dynamics may also help elucidate neurodegenerative diseases, as it is clear that fission and fusion of mitochondria have a prominent role in the development of these diseases. Also research of involvement of mitochondria in ageing is important. Reactive oxygen species are involved, but a causal role for reactive oxygen species in mitochondria in ageing has still not been found. Mitochondria have an age of approximately 1.5 billion years and many question concerning mitochondria are still unanswered. However, the list of unanswered question shortens and the true identity of mitochondria will be found in the near future.