Submitted by Penny Peck on Thu, 09/10/2025 - 22:00
New research carried out by members of Patrick Chinnery’s group has been published in Science.
The article, “Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations” explains how mitochondrial mutations can overcome the intrinsic cellular quality control systems to cause disease and how to pharmacologically revert this process.
This is the first small molecule pre-clinical candidate (in mouse models) for treatment, and it shows potential for the clinical treatment of heteroplasmic mitochondrial disease – which is currently incurable.
Mitochondrial mutations cause devastating disease in 1:8000 people and are found in many common diseases (Parkinson’s disease, cancer, diabetes). They also appear as natural genetic variation, that distinguishes individuals in different populations and organisms from different species. This paper gives the first direct evidence for how certain pathological mitochondrial mutations are inherited during evolution, therefore changing the way we think about evolution, that progresses when new mutations appear.
This project was funded by the Wellcome Trust, the Medical Research Council, the BBSRC and LifeArc.
Publication reference:
Michele Frison et al. Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations. Science 390,156-163(2025). DOI:10.1126/science.adr5438