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Heteroplasmy means that a cell contains more than one version of mitochondrial DNA (mtDNA). Because cells carry many mtDNA copies, the versions can occur in different proportions. Those proportions may shift as mtDNA replicates and is distributed among cells, and they can differ among eggs and children in the same maternal family.
What is mitochondrial DNA heteroplasmy?
A cell can contain many copies of mtDNA. If those copies include different sequences or genotypes, the cell is heteroplasmic. If its mtDNA copies share the same genotype, it is homoplasmic. The term describes the mix of mtDNA copies; it does not, by itself, say whether a variant causes disease.
For example, a cell may contain both a common mtDNA sequence and a variant sequence. Its heteroplasmy level is the proportion of copies carrying that variant in the sample being measured. That proportion is not necessarily the same in every cell or tissue.
Why can mitochondrial DNA vary between cells?
Random replication and segregation
As cells grow and divide, mtDNA copies replicate, mitochondria turn over, and copies are distributed among organelles and daughter cells. This distribution is not perfectly even. Random sampling can leave one cell with a higher proportion of a variant and another with a lower proportion, a process often described as stochastic segregation or genetic drift.
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Repeated over time and across cell divisions, these chance shifts can produce cell-to-cell differences within the same person. The 2026 review by Cameron Ryall, Patrick F. Chinnery, and Jelle van den Ameele describes this variation as arising from stochastic processes including relaxed replication and vegetative segregation, with genetic bottlenecks amplifying it.
Selection can shift proportions too
Chance is not the only influence. Selection can favor or disfavor mtDNA variants through processes such as differences in cell competition, mitochondrial removal (mitophagy), or replication. The direction and strength depend on the variant and biological setting; a variant does not inevitably rise or fall in every person or tissue.
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Can siblings inherit different levels of a mitochondrial mutation?
Yes. Human mtDNA is predominantly inherited from the mother, but a mother’s eggs need not all carry the same proportion of a variant. During germline development, a mitochondrial genetic bottleneck and subsequent segregation can sharply change which mtDNA copies, and what mix of them, end up in an egg. As a result, children of the same mother can inherit different heteroplasmy levels.
This is not ordinary Mendelian inheritance in which a fixed percentage is passed unchanged to each child. The bottleneck helps explain why proportions can vary between eggs and offspring, although the details of how the bottleneck works are still an area of study.
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Does heteroplasmy change over time or between tissues?
It can. Differences in cell turnover, replication, segregation, and selection mean that heteroplasmy may vary from one tissue to another and may shift over time. A measurement from blood, for instance, describes the tested blood sample; it does not establish the proportion in muscle, brain, or every other organ.
Some pathogenic mtDNA variants affect cell function only when their proportion exceeds a relevant threshold. There is no universal cutoff: the level associated with impaired function depends on the specific variant and biological context. A percentage alone therefore cannot establish a diagnosis or reliably predict an individual’s symptoms.
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What does a heteroplasmy percentage mean?
A heteroplasmy percentage is the measured share of mtDNA copies in a particular sample that carry the variant being assessed. It should be interpreted alongside the tissue sampled, the assay used, and the variant’s clinical context. It is not a body-wide percentage or a stand-alone measure of disease severity.
Sequencing can detect and quantify mtDNA variants, but results depend on sampling and technical interpretation. One challenge is that nuclear mitochondrial DNA segments, or NUMTs, are pieces of mtDNA-like sequence located in nuclear DNA; they can resemble genuine mtDNA variants and complicate analysis. The 2021 review by Plazzi and colleagues discusses this potential source of misinterpretation.
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For an individual result, a qualified genetics or medical professional can explain what the assay measured and whether the finding is relevant to the person’s health or family context.
Quick Recap
How the main mechanisms differ
| Mechanism | What changes | Why it matters |
|---|---|---|
| Stochastic segregation | Random distribution of mtDNA copies can raise or lower a variant’s proportion in different cells. | Helps explain cell-to-cell and tissue differences. |
| Germline bottleneck | The mtDNA mix transmitted through egg development can differ substantially among eggs. | Helps explain why children of one mother may inherit different variant proportions. |
| Selection | Biological processes may favor or disfavor a variant in a particular context. | Can drive directional shifts, but the direction is not universal. |
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