Modulating Mitochondrial Quality Control
A WRH Research Group operates within our department's Reproductive Health & Genetics theme and is run by Prof Jo. Poulton
Mitochondria research
Why this project is important?
Mitochondrial diseases can cause serious, progressive illness in children and adults. At present, there are no cures. Families affected by mitochondrial disease face difficult choices when planning to have children, as traditional approaches such as mitochondrial donation are highly specialised, not widely available, and may not be acceptable to all families.
By focusing on mitochondrial quality control and how mtDNA is transmitted across generations, this research addresses a critical gap: finding less invasive, more widely applicable options that could prevent disease transmission. Understanding the role of mitochondrial variants in common diseases such as diabetes and heart disease also means that this work could have much broader health benefits beyond rare inherited conditions.
How this Mitochondrial research can help
This research has the potential to:
Improve reproductive choices: By refining genetic counselling and preimplantation diagnosis, families at risk can make informed decisions and reduce recurrence risks.
Identify new treatments: By discovering drugs that enhance mitophagy and mitochondrial quality, we may be able to develop therapies for currently incurable mitochondrial disorders.
Inform wider health strategies: Insights into how mitochondrial variants contribute to diabetes, heart disease, and aging could lead to preventive strategies that benefit millions of people.
Reduce health costs: Even modest reductions in the burden of diseases like diabetes could have a major impact on health systems such as the NHS.
Video: Babies from 3 peoples DNA prevents hereditary diseases
Mitochondrial breakthroughs: How science is helping prevent inherited disease Eight babies have now been born in the UK using a cutting-edge IVF technique that prevents the transmission of mitochondrial disease.
Prof Jo Poulton, a leading expert in mitochondrial genetics at the University of Oxford, has long contributed to advancing our understanding of these diseases and potential treatments.
Quality Matters – Mitochondrial DNA Quality Control
Mitochondria are in a constant cycle of fission and fusion, maintaining a healthy population within the cell. Mitophagy, the recycling of damaged mitochondria, is thought to be a key quality control mechanism for mitochondrial DNA. Dysfunctional mitochondria are separated by fission and then degraded through autophagy.
We have developed high-throughput imaging techniques1 using fluorescent markers targeted to mitochondria (DS-red) and autophagosomes (GFP). These tools allow us to study mitophagy in:
the normal development of pre-implantation embryos,
mitochondrial diseases associated with mitochondrial DNA mutations3, and
conditions of excessive mitochondrial fragmentation.
We are now identifying pharmacological modulators of mitophagy that could be used to treat patients with mitochondrial disease.
Diseases of mtDNA Maintenance
Mitochondrial proteins encoded by nuclear DNA are essential for mtDNA maintenance. Mutations in these nuclear genes can cause defects leading to severe disease. For example, mutations in POLG, ANT1, and Twinkle are associated with progressive external ophthalmoplegia (AdPEO) with multiple mtDNA deletions, while mutations in TK2 and dGK cause mtDNA depletion syndrome (MDS), a devastating early-onset disorder.
Our research focuses on the basic mechanisms of mtDNA maintenance, examining how mutations affect mtDNA replication, nucleoid structure, and cell function. This work has implications for age-related diseases such as type 2 diabetes, where mtDNA defects play a role. By understanding nuclear–mitochondrial interactions, we aim to develop rational therapies for currently incurable mtDNA diseases.
Multifactorial Diseases – The OriB Variant
Common diseases such as diabetes and cardiomyopathy are linked to mtDNA variants, notably the OriB variant. This variant is present in:
- 8% of UK Caucasians,
- 50% of Pima Indians
- 95% of Polynesians.
The OriB variant has been associated with:
- type 2 diabetes,
- thinness up to middle life,
- high placental weight,
- iron loading in haemochromatosis
- dilated cardiomyopathy
- deafness.
Our collaborators have shown that this variant maps precisely to a novel origin of mtDNA replication and influences glucose uptake and mtDNA segregation in cells. Unlike many polymorphisms, the OriB variant has arisen independently in different populations, highlighting its likely functional role.
Even a modest reduction in the health burden of diabetes would have profound implications, as it is one of the largest costs to the NHS. Understanding how mtDNA variants contribute to multifactorial disease may therefore lead to preventive strategies and new therapies.
Mitochondria (green) generate energy in cells. The blueprint of the cell is stored as DNA code in nuclei (blue). Lysosomes (red) clean up damaged components including spent mitochondria.
mtDNA Transmission and Recurrence Risks
The risk of transmitting a mtDNA disorder is difficult to predict due to the mitochondrial bottleneck: a process where the number of mtDNAs passed to the next generation is drastically reduced, leading to variability in mutant load and clinical outcome.
Our group was the first to study the mitochondrial bottleneck in normal human oocytes. We have pioneered genetic counselling based on oocyte sampling, providing patient-specific recurrence risks and improved reproductive outcomes.
Working with Prof. Dagan Wells, an expert in embryo genetics, we are now offering preimplantation genetic diagnosis (PGD) for some mtDNA diseases.
We also led the development of the international consensus on reproductive options in mitochondrial disease (Poulton J. et al, Neuromuscular Disorders, 2019).
Download: Modulating mitochondrial quality in disease transmission
Useful links
Reproductive Medicine & Genetics
Our Reproductive Medicine & Genetics research covers the following research groups: Assisted Reproductive Technology (ART); Endometriosis; Fertility Preservation; Miscarriage; Oocytes and Ovaries; Pain in Women; Rhino Fertility Project and Sperm.
Study with us
We run three world class Postgraduate study programmes: MSc in Clinical Embryology (1 year residential programme) MSc by Research (2 years research degree) and DPhil (3-4 years research degree). We also teach the fundamentals of Obstetrics & Gynaecology to clinical undergraduate students as part of their medical degree.
Mitochondrial Disease
In nearly every cell in the body, mitochondria are responsible for producing energy (called ATP). They are like power stations, supplying the energy our cells need to function.
Latest publications
Physiological and biological response to heat exposure in pregnancy: a systematic review and meta-analysis.
Journal article
Bonell A. et al, (2027), Lancet Planet Health
CleanCTG: A deep learning model for multi-artefact detection and reconstruction in Cardiotocography
Journal article
Wong S. et al, (2026), Biomedical Signal Processing and Control, 123, 110654 - 110654
Dose-effect analysis of facial bone morphology following radiation therapy for head and neck rhabdomyosarcoma
Journal article
Hol MLF. et al, (2026), Radiotherapy and Oncology, 222
A blueprint of an integrated cardio-obstetric preconception care pathway for women with pre-pregnancy intermediate- to high-risk cardiovascular disease
Journal article
Vanharen Y. et al, (2026), European Journal of Obstetrics and Gynecology and Reproductive Biology, 324
Patient specific in vitro follicle development in response to ovarian freezing and culture
Journal article
Kuscu N. et al, (2026), Reproduction and Fertility
The research team
How can you help?
You can support the ongoing research into Mitochondrial through donations, collaborations and research support. If you wish to support our work, please contact us or email Prof. Jo Poulton using the button below.