Mitochondrial DNA Depletion Syndrome 13 (MTDPS13) is a rare and devastating mitochondrial disease that causes the loss of healthy mitochondria, leading to severe energy deficiency throughout the body and often resulting in early death. Currently, there are no effective treatments available.

A new study led by the Ganley Lab, in collaboration with Professor Kei Sakamoto (University of Copenhagen) and Professor Robert Taylor (Newcastle University), offers a way forward in potentially treating this disease. MTDPS13 is driven by the excessive removal of otherwise healthy mitochondria via the cell’s recycling machinery, a process known as mitophagy. Using patient-derived cells and a mouse model of the disease, the team demonstrated that activating a natural cellular energy sensor called AMPK can suppress this harmful process, allowing healthy mitochondria to be preserved and restoring their ability to produce energy.

Importantly, this was achieved using small-molecule AMPK activators, highlighting AMPK as a realistic and potentially druggable therapeutic target. These findings provide a new treatment strategy for MTDPS13, which is currently incurable, and offer hope that therapies aimed at protecting mitochondria could improve outcomes for affected patients.

The study is published in the journal EMBO Molecular Medicine and can be read here.