Mitochondrial Disease

What happens when mitochondria don't work properly?

Mitochondria are central to our health

Mitochondria are central to how our cells work and contribute in all sorts of ways to our well-being. In addition to their main role in making the energy stored in food available to power our bodies, mitochondria are also central to how cells are put together and die, how they respond to infections and injury, and in the changes that lead to cancer and ageing. Consequently, damage or disruption to mitochondria underlies many human pathologies and diseases. These range from genetic disorders that affect how mitochondria are made, to acute injuries such as heart attack and stroke, and on to chronic disorders such as obesity and diabetes and degenerative conditions such as Parkison’s and Alzheimer’s diseases. Therefore a better understanding of how mitochondria work and why they stop working well in disease is vital so we can develop new treatments for many diseases.

The work of the Mitochondrial Biology Unit is focussed on improving this understanding and on using the knowledge to develop new types of therapy for diseases involving mitochondrial damage.

How mitochondrial damage contributes to human diseases

The mitochondrial damage that causes disease can be divided into two broad categories, primary or secondary damage. The primary category is due to genetic defects in the DNA within mitochondria (mitochondrial DNA) or to a defect in a gene in the cell nucleus that is important for mitochondrial function. These genetic defects mean that mitochondria are incorrectly assembled or do not work properly. Often these “mitochondrial diseases" show up in babies or young children, and affect the brain, heart or other essential organs that use a lot of energy. However, there are many other forms of mitochondrial disease that show up in adults, for example leading to blindness or diabetes.

The other type of mitochondrial disorders, secondary mitochondrial dysfunction, is caused by damaging events during the patient’s lifetime. For example in a heart attack the damage is started by a blockage in a blood vessel in the heart, but this kills cells of the heart by disrupting their mitochondria. Similarly, there is a wide range of other disorders in which mitochondrial damage plays a significant role, including sepsis, neurodegenerative diseases, obesity, organ transplantation, cancer, autoimmune diseases, ageing and diabetes. Therefore mitochondrial damage is central to many of the most serious disorders facing our ageing population.

Therapies for mitochondria

As mitochondria are central to so many important diseases they are an important target for new therapies and drugs. Surprisingly, mitochondria have long been neglected by the pharmaceutical industry and overcoming this oversight is a key goal of the MBU.

Some of the ways we are investigating are to address the genetic defects causing primary mitochondrial diseases by developing gene therapies that replace the defective gene in the nucleus. A related approach is to treat the disease by replacing, repairing or "switching off" the damaged gene inside the mitochondria. Complementary approaches are to try and develop drugs that prevent the damage associated with mitochondrial diseases. For example, the MBU is developing drugs that are designed to go to mitochondria in patients in order to block damage in heart attack or stroke.

Finally, the MBU is also investigating new methods to measure how well mitochondria are working so that we can diagnose damage more easily and also detect whether a new treatment has worked or not.

Finding out more

There are a number of places you can find out more about mitochondria and mitochondrial disease. We can recommend: