What do mitochondria do?

They make energy.

Mitochondria are often referred to as the powerhouses of the cells. They generate the energy that our cells need to do their jobs. For example, brain cells need a lot of energy to be able to communicate with each other and also to communicate with parts of the body that may be far away, to do this substances need to be transported along the cells, which needs lots of energy. Muscle fibres also need a lot of energy to help us to move, maintain our posture and lift objects.

Mitochondria generate chemical energy, similar to the type of energy you get from a battery. The energy made by the mitochondria is in the form of a chemical called adenosine triphosphate or ATP for short. ATP is an energy currency that every cell in our body can use and it keeps us alive. The machinery that the mitochondria use to make ATP is called the electron transport chain. This chain is made up of 4 complexes which are groups of proteins that work together to carry out their function, the 5th complex is responsible for the final step of the energy generation. It is found in the inner mitochondrial membrane and parts of the first, third, fourth and fifth complexes are coded for by the mitochondrial DNA. In order for energy to be generated several steps have to occur.

Electrons are particles within an atom that are negatively charged, along with the other particles (protons and neutrons) they make up everything in the universe and they are very important in biology. Electrons are passed between the complexes of the electron transport chain and enable the cells to generate energy. The first complex accepts the electrons that are produced from the degradation of the food we eat. As it passes the electrons to the third complex in the chain protons (positively charged hydrogen atoms) are moved across the inner mitochondrial membrane. At complex three the electrons from complex one are joined by others donated by complex two. Complex three passes these electrons onto complex four and in the process moves more protons across the inner mitochondrial membrane. Within complex four the electrons are joined to oxygen to produce water, alongside one final movement of protons. Since so many protons have now been moved across the membrane the amount of them is higher on one side of the membrane than the other, this creates a gradient. Complex five then uses this gradient to produce ATP. The proton gradient rotates this final complex and with each rotation an ATP is made. For every cycle of the electron transport chain over 30 ATPs are produced, this shows how efficient energy generation is within the mitochondria.

They help maintain the environment within our cells.

The environment within our cells is closely monitored and maintained at the optimum conditions. Mitochondria are crucial to help preserve this environment and their most valuable contribution to this process is that they take up calcium. Calcium is important within cells as a signalling molecule, but this we mean that similar to flares or a 999 call calcium  alerts the cell that something needs to happen, a process needs to begin and the cell needs to respond to what is happening. This signalling needs to be regulated and so the mitochondria store calcium and release it when it is required. Too much free calcium within the cell would be detrimental to the finely tuned regulation of processes within the cell.

Where do they come from?

Mitochondria were not always resident within another cell; they were once organisms in their own right. When survival became tough they formed a relationship with another organism and they both benefitted. One gained the ability to use oxygen to produce energy, while the other gained protection against predators.  This relationship has lasted for billions of years and has allowed multi-celled life forms to become bigger and more complex. We call this the endosymbiotic theory, which comes from the Ancient Greek words  for ‘to live within together’.

Our story begins 2 Billion years ago. . . . . . . .

The earth was still developing and changing, life was becoming more complex. The earliest life on earth survived by breaking down the compounds around them into something less complicated (by a process of fermentation) which generated energy that they could use to survive and reproduce. Fermentation can only occur when there is no oxygen present.

However, a new type of cell was developing that could use light to generate energy (by a process of photosynthesis), in the same manner that plants do today. This process uses carbon dioxide and produces oxygen. These cells were increasing in number at an alarming rate and because of this the concentration of oxygen in the atmosphere was increasing. This was bad news for the organisms that relied on fermentation, or that could not tolerate high oxygen levels.

It was good news however for organisms such as Rickettsia prowazekii (let’s call them Ricke for short!). These bacteria belong to a family of bacteria called the α-proteobacteria and are the bacteria responsible for human Typhus, a disease estimated to have killed 20-30 million people in the years following the First World War. Billions of years ago, Ricke had the advantage, they could use oxygen to produce energy to survive and reproduce. However Ricke is a small bacterium (less than one thousandth of a millimetre in size) and was probably consumed by other organisms. All life on earth had to adapt to survive and exist within the changing atmosphere.

It is likely that at some point Ricke were taken up by a larger host cell but was not broken down. The host cell could now survive since Ricke provided a way to produce energy that used the increasing levels of oxygen within the atmosphere.  The benefit for Ricke was the protection from other predatory cells. This mutually beneficial relationship has lasted for millennia.

Over the past billion years Ricke has changed and become what we now call mitochondria. It has lost most of its independent function and much of it’s DNA to the nucleus of the host cell. A small amount of DNA however has been retained by  mitochondria and it uses this DNA to make the components necessary to produce energy. The mitochondria could now no longer survive as an independent organism and relies entirely on the host cell to carry out its functions.

There is a lot of evidence to support this theory for the origin of mitochondria, this evidence includes;

  1. The fact that the DNA contained within mitochondria is circular which is different to the DNA on our chromosomes and is similar to the DNA found within bacteria.
  2. Mitochondria have two membranes.
  3. The DNA contained within the mitochondria is very similar to the DNA of Ricke but is much smaller, due to the donation of information to the nucleus.

Without this relationship, these mitochondria and their energy generation, organisms would not have been able to grow bigger and become more complicated. In short we would not be here today.

What do they look like?

For many decades mitochondria were believed to be shaped like a baked bean, and when we look under high powered microscopes at the mitochondria they often do. Mitochondria have two membranes (protective coverings) one surrounding the other, called the inner and outer mitochondrial membranes. The inner membrane is highly folded and forms structures called cristae, the machinery for energy generation can be found on these cristae. Between the two membranes is a gap called the inter membrane space, while the space at surrounded by the inner mitochondrial membrane is called the matrix. The matrix contains the mitochondrial DNA, the components for the mitochondria to carry out their functions and the machinery needed to make new copies of the mitochondrial DNA.

Image and diagram of Mitochondria

However mitochondria are often not found like this and the majority of the time they join together to form beautiful branched networks that fill the cell they are in (see picture below). These networks are constantly changing and reshaping. We think that the mitochondria form networks to allow the contents of the matrix to mix. In cells that are dying or that contain mitochondria which are not functioning properly then the network breaks down and the mitochondria once again take on their ‘bean’ like appearance. The network reaches to the limits of the cell in all directions, but it varies in appearance in different cells. In brain cells for example around the nucleus the mitochondria form a network but in order to be transported to the end of the nerve which might be far away the mitochondria return to being ‘bean’ shaped and are transported along a long fibre called an axon. We can record movies of this happening and use measurements of how fast the mitochondria move, how many are moving and in which direction they travel in our research.

How Mitochondria look

What is mitochondrial DNA?

We have all heard about the DNA that is found within our chromosomes, this DNA determines the all our physical characteristics (eye colour, hair colour, height etc) and the vast majority of the components (called proteins) that make our cells and bodies work. But not all the DNA within our cells is found in the nucleus, there is some DNA within the mitochondria. This DNA is much smaller than the DNA within the chromosomes, it contains only 16,500 base pairs compared to over 3 billion pairs in the nuclear DNA. Base pairs work like magnets to hold the two strands of DNA together, the bases form the ‘letters’ of the DNA which when read correctly can be translated into the proteins that the cells need to function.  The DNA within the mitochondria forms a circle, similar to the DNA within bacteria, and different to the DNA within the chromosomes. While each cell contains only two copies of each chromosome each mitochondria contains many copies of the mitochondrial DNA and there are many mitochondria in each cell.

Why is mitochondrial DNA important?

Mitochondrial DNA contains vital information that allows the mitochondria to make the proteins it needs to make energy. It contains 37 genes compared to the thousands of genes found within the chromosomes, but all these genes are vital for making the mitochondria and hence our cells work properly. None of the genes within the mitochondrial DNA control your appearance but when these genes contain mistakes (mutations) because of the important job that mitochondria do they cause disease.

Maternal inheritance

The DNA contained within our chromosomes comes from both our parents. Our cells contain 23 pairs of chromosomes, so 46 in total. Each egg and sperm contain 23 chromosomes which are not paired, upon fertilisation the pairs of chromosomes join together so half your DNA comes from your mother and half from your father. But when it comes to mitochondrial DNA the situation is slightly different. Although both sperm and egg cells contain mitochondria, the mitochondria from the sperm are broken down shortly after fertilisation, which means that all the mitochondria, and all the copies of the mitochondrial DNA in the fertilised egg are from the mother.  This means that since children inherit their entire mitochondrial DNA from their mothers it follows that it is only women that can pass on the mutations within this DNA that cause disease.

Heteroplasmy

Mitochondria Heteroplasmy DiagramSince there are many copies of mitochondrial DNA within each cell it means that the situation may arise where some copies may contain detrimental changes (mutations) in the code of the DNA whereas others will carry the right code, we call this wild type.  This mixture of mitochondrial DNA copies with mutations and wild type copies is called heteroplasmy and the maintaining the balance so that the cell has enough wild type copies is important for the cell. Cells will only be affected if the percentage of its mitochondrial DNA copies that carry a mutation exceeds a certain limit, this is called the threshold. In most cells the threshold is between 50-60%, once this level is exceeded the cell will show signs of mitochondrial dysfunction.

 

 

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