Mitochondria are essential organelles that supply cellular energy and regulate many fundamental processes, including metabolism, signalling and cell survival. Defects in mitochondrial structure and function cause a wide range of inherited and acquired disorders affecting multiple organs, including the brain, liver, heart and muscle. Despite their clinical importance, the molecular mechanisms linking mitochondrial dysfunction to tissue-specific disease remain poorly understood.

We combine fundamental mitochondrial biology with advanced stem cell models to understand how defects in mitochondrial architecture lead to disease and to identify new therapeutic strategies.

1. Mitochondrial architecture and function

We investigate the molecular mechanisms that govern mitochondrial architecture and function, with a particular focus on the mitochondrial contact site and cristae organising system (MICOS) complex. Our work focuses on MIC13 and its interaction partners, including SLP2, to understand how cristae architecture is established and maintained, and how defects in mitochondrial structure influence mitochondrial function and cellular metabolism.

2. Mitochondrial disease modelling

We develop genome-edited induced pluripotent stem cell (iPSC) models carrying patient-specific disease-causing mutations and differentiate them into disease-relevant cell types, including hepatocytes and neurons. These models allow us to investigate mitochondrial diseases in a physiologically relevant human context.

As a disease paradigm, we investigate MIC13-associated mitochondrial hepato-encephalopathy, a severe multisystem disorder caused by defects in mitochondrial cristae organisation. Using these models, we study how structural changes in mitochondria drive metabolic dysfunction, tissue-specific pathology and disease progression.

Our work hasr evealed a direct link between mitochondrial architecture and cellular metabolism, demonstrating that defects in cristae organisation lead to profound metabolic rewiring and early pathological changes. We are particularly interested in understanding how mitochondrial structure regulates cellular metabolism, stress adaptation and extracellular matrix (ECM) remodelling during disease.

3. Mechanism-based therapeutic strategies

By combining disease models with imaging, biochemical and multi-omics approaches, we aim to identify disease mechanisms and metabolic vulnerabilities that can be targeted using mechanism-based therapeutic strategies and future high-throughput screening approaches. In the long term, we aim to develop targeted metabolic interventions and establish platforms for therapeutic discovery in mitochondrial disease.