Current topics
- Purifying selection of mitochondrial DNA
- Ageing
- Mitochondrial and nuclear crosstalk
- Mitochondrial phosphoproteomics
Research focus
Mitochondria are vital cellular organelles responsible for producing the majority of adenosine triphosphate (ATP) via oxidative phosphorylation, a process essential for sustaining cellular function and organismal viability. In addition to their central role in energy metabolism, mitochondria participate in diverse cellular functions including intermediary metabolism, calcium homeostasis, apoptotic signaling pathways, and the biosynthesis of critical biomolecules. Notably, mitochondria contain their own circular genome, which encodes a limited subset of proteins essential for respiratory chain function. Proper mitochondrial activity depends on the coordinated expression and integration of both mitochondrial-encoded and nuclear-encoded gene products. This tight regulation of mitochondrial and nuclear genomes is fundamental to maintaining cellular homeostasis and overall physiological health.
When mitochondrial function is impaired, e.g. due to mutations in the nuclear or mitochondrial genome, it can have profound effects on human health. Mitochondrial dysfunction is implicated in a wide range of pathologies, including mitochondrial diseases, aging, cancer, neurodegenerative conditions such as Parkinson’s and Alzheimer’s disease, cardiovascular disease, and metabolic syndromes. Because mitochondria are involved in critical cellular signaling pathways, their malfunction often triggers systemic consequences, making them a key focus in understanding disease mechanisms.
Despite their critical roles, many aspects of mitochondrial biology remain poorly understood. We still lack fundamental insights into how mitochondrial DNA is inherited and maintained throughout life, and the molecular functions of more than half of mitochondrial proteins are yet to be defined. Moreover, it remains unclear why mitochondrial dysfunction results in such a broad and complex range of clinical symptoms.
To decode the molecular systems that govern mitochondrial genetics and function, and to uncover how their disruption contributes to human disease, our research group employs a comprehensive multiomics approach. By integrating ultradeep mitochondrial DNA sequencing with transcriptomics, proteomics, and mitochondrial-specific phosphoproteomics, we generate high-resolution datasets that provide a systems-level view of mitochondrial function. These approaches, applied in cellular and animal models of human disease, allow us to uncover novel regulatory mechanisms and identify therapeutic targets. Our ultimate goal is to translate these insights into strategies for the diagnosis, prevention, and treatment of mitochondrial-related diseases.