Mitochondrion - much more than an energy converter

Mitochondria are organelles that are virtually cells within a cell. They probably originated billions of years ago when a bacterial cell was engulfed when visiting what was to become a host cell. The bacterial cell was not digested and stayed on in symbiotic relationship.
A true story of a visitor that stayed on and on……for ever. Like many visitors the guest bacterium contributes something towards its keep; the mitochondrion has certainly made sure its presence is felt. In addition to the features mentioned below mitochondria also take part in reactions concerning fatty acid metabolism, the urea cycle and the biosynthesis of the haem part of haemoglobin

Click here to view an image of mitochondria interpreted using the Gridpoint cross-hairs device

Mitochondria: the energy converters
Mitochondria, using oxygen available within the cell convert chemical energy from food in the cell to energy in a form usable to the host cell. The process is called oxidative phosphorylation and it happens inside mitochondria. In the matrix of mitochondria the reactions known as the citric acid or Krebs cycle produce a chemical called NADH. NADH is then used by enzymes embedded in the mitochondrial inner membrane to generate adenosine triphosphate (ATP). In ATP the energy is stored in the form of chemical bonds. These bonds can be opened and the energy redeemed.

In return the host cell provides physical protection and a constant supply of food and oxygen.

Mitochondrial cells divide using their own circular strand of DNA and as a result there can be many mitochondria in one cell. In cells where there is a high energy demand large numbers of mitochondria are found.
The tail of a sperm contains many mitochondria and they run in a spiral like form along the length of the tail. In heart muscle cells about 40% of the cytoplasmic space is taken up by mitochondria. In liver cells the figure is about 20-25% with 1000 to 2000 mitochondria per cell.

Mitochondria: determinators
Recent research indicates that in addition to converting energy mitochondria play quite a large part in determining when a cell will die by ordinary cell death (necrosis) or programmed cell death (apoptosis). In apoptosis the mitochondrion releases a chemical, cytochrome c, and this can trigger programmed cell death (apoptosis).

Mitochondria are also thought to influence, by exercising a veto, which eggs in a woman should be released during ovulation and which should be destroyed by programmed cell death (apoptosis). This is part of a process called atresia. It appears that in this process mitochondria and the nucleus of the cell in which the mitochondria reside, are screened for biochemical compatibility. The pairs that are incompatible are shut down by programmed cell death.

Mitochondria: generators of disorders and disease
Mitochondria are very important energy converters. In this process they produce waste products. In mitochondria these are called reactive oxygen species (ROSs). and include 'free radicals'.

ROSs can damage DNA Mitochondrial DNA is no exception and since it is located so close to the energy converters it can be heavily attacked, sometimes mutating ten times faster than nuclear DNA in an ordinary cell.
These mutations are the source of mitochondrial disease that can affect areas of high energy demand such as brain, muscles, central nervous system and the eye. People suffering from Parkinson's or Alzheimer's disease have a much higher mitochondrial mutation rate than do healthy people and so the functioning of mitochondria may be implicated in these diseases.
Mutations caused by ROSs have been suggested as contributing to the ageing process. Many more mutations in mitochondrial DNA take place in people over 65 than in younger people, but many more factors are involved in this inevitable (at present) but variable process.
The working of mitochondria at a molecular level is also involved in the good (or otherwise) progress of people in the very early stages of recovery following open heart and transplant surgery.
In nearly all these 'disorder' states it is very likely that other factors, such as genetics, are also involved.
Recent work is linking several severe side effects of treating HIV with the treatment drugs AZT and 3TC. It appears that the drugs damage mitochondria and block the production of mitochondrial DNA.

Mitochondria: the enhancer
Fruit flies that have been genetically engineered to detoxify ROSs live up to 40% longer than normal controls. French and Japanese centenarians appear to have advantageous mutations in their mitochondrial DNA. In the French the variant was found in 14% of the centenarians compared with 7% of the whole population. 62% of the Japanese centenarians had advantageous mitochondrial DNA compared with 45% of the general population. This is interesting but since we do not know about cause and effect, care needs to be exercised when considering these figures.

In the field of sport it is not difficult to reason that athletes with high counts of mitochondria in their heart and other appropriate muscle cells are able to do just that little bit better than others less well endowed.

Mitochondria: providers of genetic history
Mitochondria are virtually cells within a cell and each one has its own DNA. Mitochondrial DNA is only inherited through the maternal line. Any mitochondrial DNA contributed by the father is actively destroyed by programmed cell death after a sperm fuses with an egg. This interesting situation has provided geneticists and anthropologists with a very useful analytical and measuring tool.

Over the years maternal mitochondrial DNA has been inherited in a direct line never having been combined or shuffled with DNA from mitochondria of the male line. Through analysis of mitochondrial DNA from an ethnic mix, genetic evidence supports the idea that the main pool of our ancestors came 'out of Africa' about 200,000 years ago and that we did not descend from Neanderthals. Our mitochondrial DNA has descended from a common ancestral group of "Mitochondrial Eves" or "African Eves". Some people are sceptical about this idea but strong evidence in support of it is accumulating.

Mitochondria: an organelle probably used to boost the success rate of infertility treatment.

"Babies born with two mothers and one father" was how one British national newspaper ran the story about a controversial method, outlawed in the U.K., in which cytoplasm including mitochondria from the cells of a younger woman are introduced into the eggs of an older woman seeking IVF infertility treatment. The technique called ooplasmic transplantation seeks to correct disorders, possibly associated with the mitochondria, in the egg. The mitochondrial DNA will be incorporated into the cells forming the embryo and for this reason it is the first example of germline gene therapy. There are concerns about possible long-term side effects, which could be passed on to subsequent generations. Although the technique is opposed by many, proponents argue that they are not 'tampering' with nuclear DNA and that the procedure has helped women of some 30 children worldwide to become mothers.

This is an image of:

A mitochondrion is typically about 0.5um in diameter, the size of some bacteria. It can be identified using a good light microscope by the 'threads dotted with grains' that appear to run across the diameter of the organelle. It is from this appearance that the name 'mitochondrion' is derived from the Greek mitos meaning thread and chondrion meaning a grain. In the early days of cell biology research mitochondria were teased from cells using fine needles.

Internal Structure and Function
The internal structure of a mitochondrion is not dissimilar to a chloroplast in that both organelles have two membranes. In mitochondria the outer membrane is thought, in effect to be derived from that part of the cell membrane of the eucaryotic cell that formed the vesicle containing the engulfed the visiting bacterium. The inner membrane, now much folded, is thought to be the cell membrane of the engulfed bacteria.

The very folded inner membrane provides a very large surface area on which reactions can take place (a lot of laboratory bench space).

The folds called christae are produced when the membrane folds in from the side. The space bounded by the inner membrane is called the matrix. This contains chemicals and structures including mitochondrial DNA and small ribosomes.

The matrix side of the folded membrane is dotted with structures that resemble ordinary electric light (lamp) bulbs in lamp holders. It is in these protein structures, sometimes called stalked particles, that a flow of protons through the christae from the inner membrane to the matrix enables adenosine diphosphate (ADP) to be converted to adenosine triphosphate (ATP). Adenosine triphosphate 'stores' energy in a chemical bond and in this form it can be distributed and utilised throughout the cell. It is similar to electrons coming along a wire to the electric light bulb when energy is changed to light energy but this is an analogy and should not be taken too far.

SUMMARY

Mitochondria are large organelles found in the cytoplasm of all plant and animal cells. They are though to have originated as a result of a cell engulfing a small bacterium and then the two units living in a symbiotic relationship. The mitochondria reproduce within the host cell. These 'visitors' (see above) have become so essential to the life (they provide most of the chemical energy as ATP) and death (they can release a chemical that triggers programmed cell death) of a cell, that medical specialists are actively introducing them into egg cells. This is being done as part of a protocol in the treatment of infertility in humans. It is interesting to reflect on the fact that the organelle that once entered a cell by accident, is now being captured and transferred by humans and placed in the egg cells of another human being.