Connecting mitochondrial methylation potential to cellular dysfunction and disease

Mitochondria form a central hub in cellular metabolism, with a vast number of different metabolic pathways relying on their function.

Dysfunction of this organelle is increasingly linked to a broad range of disease states, as well as to normal ageing, but the underlying mechanism is not well understood.

Increasing evidence indicates that metabolism of one-carbon units, i.e. the distribution of methyl groups for the synthesis of DNA, polyamines, amino acids, creatine or phospholipids, is important in this context, and induction of the one-carbon cycle has been suggested to be an early hallmark of mitochondrial dysfunction.

My group recently demonstrated that the one-carbon metabolism by itself can affect mitochondrial function via the methylation of key mitochondrial factors, establishing a link between cellular methylation potential and energy metabolism.While our data signified the importance of methylation in mitochondrial disease, numerous aspects of mitochondrial methylation potential remain unknown.

By using a combination of animal models, patient samples, molecular biology, and proteomics this project will study the metabolic interactions and consequences of low mitochondrial methylation potential.

This will be further explored in common pathologies, as well as in patients with inborn errors of metabolism, with the long-term goal of discovering new treatment possibilities.