Glossary of Terms


Ataxia – a lack of voluntary coordination of muscle movements which may affect balance, coordination and speech.

ATP (adenosine triphosphate) – the molecule that provides the energy used by the cells of the body.

Autosomal recessive – two copies of an abnormal gene have been inherited (usually one from the mother and one from the father) and caused a disease or trait.


Biomarker – a naturally occurring molecule or characteristic that can be used to identify a particular disease.


Chromosomes – thread-like structures made up of genetic information (DNA) found within the nucleus of cells. Each cell usually has 23 pairs of chromosomes.

Complexes – components of the mitochondrial respiratory chain that are arranged into five different groups (Complex I to V).

COX – cytochrome c oxidase, complex IV of the mitochondrial respiratory chain. COX subunits are encoded in both the nuclear and mitochondrial genomes.

Creatine kinase – an enzyme found in muscle and other tissues. It uses ATP to breakdown creatine. Patient with muscle disease often show elevated levels of CK in the blood.

CRISPR/Cas – a powerful technique that is used for gene editing (see below).

Cristae – the folds of the inner mitochondrial membrane (see below).

Cytoplasm – a jelly-like substance found within cells that contains many different structures, including mitochondria.


Deletion – removal of a single chemical letter or a section of DNA. These deletions can occur in the mitochondrial DNA (see below) and are a common cause of mitochondrial disease in adult patients.

Depletion – a reduction in mitochondrial DNA. Mitochondrial DNA depletion Syndrome (MDDS) is a group of autosomal recessive disorders that have a significant reduction of mitochondrial DNA in affected tissues (e.g. muscle, liver, brain).

DNA (deoxyribonucleic acid) – the molecule that contains all the genetic information needed to make all living things. DNA contains four different chemicals represented by the letters A,T,C and G.

DNA sequence – the order of the chemical letters within DNA (see above). The DNA sequence is unique to every person and makes us who we are.

Dysarthria – difficult or unclear speech formation, usually related to changes in the brain, and not related language abilities.

Dysphagia – a medical term used to describe swallowing difficulties.

Dysphasia – a language disorder due to brain disease resulting in difficulties understanding (receptive dysphasia) or putting words together (expressive dysphasia).

Dysphonia – difficulty speaking due to physical problems with the mouth, tongue, throat or vocal cords.


Electron transport chain – part of the energy chain (complexes I-IV; see above) that is responsible for generating energy within the mitochondria.

Exon – a sequence of DNA that contain instructions to make a protein (see below).


Fatigue – a subjective feeling of tiredness often alleviated by periods of rest.

Fibroblast – a type of connective tissue cell present in the body. Skin biopsies are often taken in order to culture fibroblasts and determine mitochondrial function.

Fibroblast growth factor (FGF) 21 - a metabolic hormone (protein) found in humans that may be useful as a biomarker of mitochondrial disease.

Fission – the process by which mitochondria split apart in the cell.

Free radicals – see reactive oxygen species (below).

Fusion – the process by which mitochondria come together in the cell.


Gene – genetic ‘instructions’ within our DNA that produce the building blocks (proteins) that make up our bodies.

Gene editing – a technique that allows the order of the four chemical letters (A, T, C, G) that make up the DNA sequence to be changed. This can involve adding, replacing or removing a single letter or a section of DNA.

Gene therapy - the introduction of normal genes into cells, to replace missing or defective ones, in order to correct a genetic disorder.

Genetic bottleneck – a process that occurs during the formation of eggs that results in a limited number of mitochondria being passed to the next generation.

Genetic diagnosis – identifying a mistake within a gene (see above) that is responsible for causing a genetic disease.

Genome - the complete set of genetic information needed to make and maintain all living things.

Genotype – the set of genes carried by an individual; a mutation in a specific genotype may indicate a clinical disease.


Heteroplasmy/heteroplasmic – a mix of normal and faulty mitochondrial DNA within a cell or tissue in the body.

Homoplasmy/homoplasmic – the presence of only faulty mitochondrial DNA within a cell or tissue in the body.


Intron - a sequence of DNA that does not contain instructions to produce a protein and is found between exons (see above).




Lactate – lactic acid (a chemical found in the body, often measured in blood or spinal fluid). Lactic acidosis is the build up of lactate in the body due to problems when the body’s metabolism. Patients with mitochondrial disease may experience lactic acidosis during times of metabolic stress e.g. illness, excessive exercise, dehydration.

Leigh’s syndrome – the most common mitochondrial disease in children often associated with brain changes and developmental delay.

LHON (Leber’s hereditary optic neuropathy) – a particular mitochondrial disease which is characterised by a rapid loss of sight in both eyes.


Maternal inheritance – the situation where mitochondrial DNA is inherited from the mother only.

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes) – the most common mitochondrial disease caused by a mutation in mitochondrial DNA.

Metabolic disorder – a condition that disrupts the normal process of making energy from the food we eat due to abnormal chemical reactions that in the body.

MERRF (Myoclonic Epilepsy with Ragged Red Fibers) – a particular mitochondrial disease caused by a mutation in mitochondrial DNA.

Migraine – a recurring headache with associated sensory disturbances.

Mitochondria – small structures found in nearly every cell of the body that have an important role in energy production.

Mitochondrial biogenesis – the production of new mitochondria within a cell.

Mitochondrial disease – a term that covers a wide range of different diseases characterised by faulty mitochondria.

Mitochondrial DNA (mtDNA) – the DNA found within mitochondria that contains 37 genes needed for the mitochondria to function.

Mitochondrial DNA disease - a term that covers a wide range of different diseases characterised by faulty mitochondria when the genetic mistake is found within the mtDNA (see above).

Mitochondrial donation – an IVF-based treatment that can prevent mitochondrial DNA disease being passed from a mother to her child.

Mitochondrial dysfunction – a term used to describe faulty mitochondria, or mitochondria that are not working properly.

Mitochondrial membrane – mitochondria consist of two mitochondrial membranes: the outer layer that surrounds the mitochondria and the inner layer within the mitochondria. The inner mitochondrial membrane is highly folded and is the site of energy production.

Mitochondrial respiratory chain - the complete energy chain (complexes I-V; see above) that is responsible for generating energy within the mitochondria.

Muscle biopsy – a procedure that involves removing a small sample of muscle to help investigate or diagnose a mitochondrial disease.

Mutation – a genetic ‘mistake’ within the DNA sequence (see above) that can cause genetic disease.

Myopathy – a medical term used to describe muscle disease.


Neuropathy – damage to the nerves. Peripheral neuropathy often causes numbness in your hands and/or feet, and can cause both weakness and pain

Next generation sequencing (NGS) – a modern and highly sensitive genomic technique that allows the entire DNA sequence (see above) to be determined.

Nuclear DNA – genetic information found in the nucleus of the cell that contains ~20,000 genes and determines all of our characteristics, eg. height, eye colour etc.

Nucleus – the part of the cell that contains the nuclear DNA (see above) and controls how the cell behaves.


Oocyte – another word for an egg cell.

Ophthalmoplegia – weakness or paralysis of one or more of the muscles within or around the eye responsible for eye movements.

Optic atrophy – a sign of damage to the optic nerve (the nerve which carries signals from the eye to the brain) which may result in visual loss. On examination the back of the eye (optic disc) appears pale.

Oxidative phosphorylation – the biochemical process that takes place in the mitochondria and produces ATP.

Oxidative damage - damage to cells when there are high levels of reactive oxygen species (see below). This damage may contribute to some of the symptoms of mitochondrial disease.


Pathogenic – disease causing.

Phenotype – a set of physical characteristics or traits resulting from the genes you have inherited.

Point mutation - a change in a single chemical letter of the DNA. These changes can occur in the nuclear DNA (see above) or the mitochondrial DNA (see above) and can both cause mitochondrial disease.

Preimplantation genetic diagnosis (PGD) – an IVF-based technique that involves testing early embryos in the lab to try and identify an embryo with a low risk of mitochondrial disease that can be transferred to the womb to try and establish a pregnancy.

Prenatal testing – a test performed on cells taken from an early pregnancy to determine the risk of mitochondrial disease in the developing baby.

Protein – the ‘building blocks’ that make up our body and are an essential part of all living things. Proteins are made of amino acids and the instructions to make these proteins are found within our DNA (see above).

Ptosis – drooping (falling) or the upper eyelid which can happen in one or both eyes.



Reactive oxygen species (ROS) - damaging chemicals that are produced by the mitochondria during normal energy production. These reactive oxygen species, also known as free radicals, may be found at higher levels within cells when the mitochondria don’t work properly.

Rearrangements – partial deletions and partial duplications of mtDNA.

Respiratory chain complexes – see complexes (above).

RNA (ribonucleic acid) – a molecule that is very similar to DNA and is present in all living cells. Its main role is to act as a messenger and copy instructions contained in the DNA which can then be made into a protein.


Seizure – sudden, abnormal electrical activity in the brain causing abnormal movements, loss or awareness or loss or consciousness.

Splicing – a molecular process in which introns are removed and exons are joined together.

Stem cell – a cell which is capable of giving rise to more cells that are the same or can become different cells of the body.

Stroke-like episode – an evolving neurological event occurring at any age driven by seizure activity and supported by evidence of EEG and MRI brain changes. These episodes are most commonly associated with the m.3243A>G mutation and POLG.


Threshold effect – the level of faulty mitochondria that must be reached within a cell or tissue for the clinical symptoms of mitochondrial disease to occur. This can vary for different mitochondrial diseases but usually ranges from 60-90%.

Transcription – the process by which DNA is copied into RNA.

Translation – the process by which RNA is used to make protein.




Whole exome sequencing (WES) – a form of next generation sequencing (see above) that allows specific genes within the DNA to be sequenced.

Wild-type – the naturally occurring version of a gene (see above) that does not contain a mutation.




Zygote – an egg just after it has been fertilised and before it divides into two-cells.