Powering the brain: an introduction to mitochondria
Professor Doug Turnbull is Director of the Wellcome Trust Centre for Mitochondrial Research. In this, his first post for ThInk, he introduces the Wellcome Trust Centre and gives a crash course in the function and dysfunction of mitochondria.
The Wellcome Trust Centre for Mitochondrial Research at Newcastle University is a major new initiative by the Wellcome Trust to improve the lives of patients with mitochondrial disease. The four major themes of the research conducted at the Centre are to understand how mitochondria make proteins, to develop methods to prevent transmission of mitochondrial DNA disease, and to investigate the underlying mechanisms of the neurological changes we see in patients and the role of mitochondrial DNA in common degenerative diseases. Our scientific studies are closely related to our clinical service since Newcastle is one of three Centres in the UK which run a specialist clinic for patients with mitochondrial disease. This service, funded through the NHS by the Highly Specialised Services, means that patients can be referred from all over the country either for diagnosis or for treatment. Patients are followed up in our clinic so that the clinical course of the disease can be tracked and the effects of any treatments can be assessed.
In the coming months, I’ll be writing more about the research conducted by the centre and the diseases which we are investigating. To begin with, however, it may be useful to explain something of the function, and dysfunction, of mitochondria in the human body.
An introduction to mitochondria
Every cell in our bodies contains mitochondria – commonly called the powerhouses of the cell. These powerhouses provide ATP, a molecule which transports chemical energy within the cell, fuelling cellular processes. This, along with other functions, means that mitochondria are essential for normal brain function. Mitochondrial dysfunction is involved in several neurodegenerative conditions, including Parkinson’s disease and Alzheimer’s disease. However, the particular interests of the Wellcome Trust Centre for Mitochondrial Research are a group of genetic diseases caused by mutations in the mitochondrial genome.
Mitochondria are unique in that they contain their own DNA. This tiny genome only codes for 13 proteins, all of which are essential for the normal function of mitochondria. The 13 mitochondrial proteins are all subunits of the oxidative phosphorylation system that is essential for the generation of ATP.
Mitochondrial DNA disease
Mutations of the mitochondrial DNA cause mitochondrial DNA disease. Such mutations are common and at least 1 in 5000 individuals has mitochondrial DNA disease. Mitochondrial DNA disease affects tissues that are heavily dependent on energy generated by mitochondria. The brain is often severely affected, resulting in a variety of different symptoms including epilepsy, strokes, deafness, vision problems and cognitive impairment.
Mitochondrial DNA is strictly maternally inherited with no contribution from the sperm. This means that mitochondrial DNA diseases are passed on from mother to child.
In many families there are multiple patients affected but the symptoms between different family members can vary markedly. The reason for this variation is not fully understood, but it can be partly explained by the nature of mitochondrial genetics.
Mitochondria are plentiful in neurons and other cells, and mitochondria all contain multiple copies of mitochondrial DNA. Thus within a neuron or muscle cell there will be many hundreds or thousands of copies of mitochondrial DNA. In most mitochondrial DNA diseases there is a situation called heteroplasmy – which means there is a mixture of both mutated and normal (wild-type) mitochondrial DNA. The proportion of wild-type DNA compared to mutated mitochondrial DNA will affect the phenotype, with those with very high levels of mutated mitochondrial DNA tending to have the more severe disease.
The Wellcome Trust Centre for Mitochondrial Research is ideally placed to research these diseases since both clinical and basic science work closely together.
The remarkable genetics of mitochondrial DNA have fascinated scientists for many years, but only now are we starting to understand the consequences for human health. The maternal inheritance of the disease presents some interesting scientific challenges, but for those families with inherited mitochondrial DNA disease then the search for better treatment or new ways to prevent transmission must be our aim.