Mitochondrial inheritance and mitochondrial DNA disease
Mitochondria carry their own small genome, passed only from the mother; how much faulty mtDNA a tissue holds decides whether and how disease appears.
Key facts
- Mitochondrial DNA is a circle of about 16 600 base pairs with 37 genes: 13 proteins of the respiratory chain, 22 transfer RNAs and 2 ribosomal RNAs. Each cell holds hundreds to thousands of copies.
- It is inherited from the mother only; an affected man does not pass mtDNA disease to his children.
- Heteroplasmy: a cell can hold a mix of normal and mutant mtDNA. Disease appears when the mutant share passes a tissue's threshold.
- A bottleneck in egg development means a mother's children can receive very different mutant loads, so recurrence risk is hard to predict.
- Most mitochondrial proteins are encoded in the nucleus, so many «mitochondrial diseases» follow Mendelian inheritance (for example POLG and SURF1 defects).
In detail
- Tissues with the highest energy needs suffer most: brain, skeletal and heart muscle, retina, inner ear, kidney tubules and pancreatic islets.
- Classic mtDNA disorders: MELAS (stroke-like episodes, lactic acidosis), MERRF (myoclonic epilepsy, ragged-red fibres), Leber hereditary optic neuropathy (painless loss of central vision, mostly in young men), Kearns–Sayre syndrome (usually a sporadic large deletion) and maternally inherited Leigh syndrome.
- The mutant load in blood can be lower than in muscle or urine, so the right sample matters when testing.
- Mitochondrial donation during IVF can prevent transmission of mtDNA disease and is permitted in a few countries.
- Also called
- Maternal inheritance, Heteroplasmy and the threshold effect
Clinical notes
- Suspect a mitochondrial disorder when several unrelated organs fail together, with lactic acidosis, deafness, diabetes or short stature, especially along the maternal line.
- Valproate can cause liver failure in POLG-related disease.
Test yourself
Think of the answer, then tap the question to see it.
Why can an affected father not transmit an mtDNA disease?
Mitochondria in the embryo come from the egg; sperm mitochondria are eliminated after fertilisation.
What is heteroplasmy, and why does it matter?
A mix of normal and mutant mtDNA in a cell; disease appears only when the mutant share exceeds the tissue's threshold.
Why are many mitochondrial diseases inherited in a Mendelian way?
Most mitochondrial proteins are encoded by nuclear genes.
Connections
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Mitochondrial DNA: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Mitochondrial DNA (National Human Genome Research Institute (NHGRI), 2026).
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Representative model, for educational purposes only.