Mitochondrial dynamics in (patho)hysiology


Normal cell functioning and survival requires energy in the form of ATP that is generated by a variety of metabolic pathways. Within this metabolism, the mitochondrial oxidative phosphorylation (OXPHOS) system is among the prime producers of ATP. Proper OXPHOS function is also required to sustain many other mitochondrial processes including the exchange of ions and metabolites with the cytosol. In this sense, the OXPHOS system plays a key role in various cellular processes like adaptive thermogenesis, innate immune responses, calcium and redox signalling, and programmed cell death (apoptosis). OXPHOS and mitochondrial dysfunction are not only associated with relatively rare monogenic mitochondrial disorders but also observed during more common pathologic conditions, such as Alzheimer's, Huntington's and Parkinson's disease, cancer, cardiac disease, diabetes, epilepsy, and obesity. In addition, a progressive decline in the expression of mitochondrial genes is observed during normal human aging and mitochondrial function is inhibited by environmental toxins and frequently used drugs.

My group focuses on gaining a quantitative mechanistic understanding of mitochondrial (patho)physiology at the (sub)cellular level during mitochondrial dysfunction. More specifically, we aim to understand the relationship between mitochondrial (dys)function, mitochondrial (ultra)structure, reactive oxygen species (ROS)-induced signaling and/or stress, and adaptive cell survival responses. When appropriate, the obtained fundamental insights are valorized in collaboration with Khondrion BV, which focuses on the rational design of novel therapeutics for mitochondrial disease. Since mitochondrial metabolism is intricately interfaced with its cellular environment, research is performed using various (patient- and animal-derived) cell models. In this sense, we have specialized in combining biochemical and molecular cloning strategies with fluorescent reporter analysis, state-of-the-art quantitative life-cell/single-molecule microscopy and spectroscopy, image processing and quantification, mathematical modeling, high-resolution respirometry and machine learning techniques. This unconventional combination of expertise bridges the gaps between researchers from different backgrounds (medical doctors, biologists, biochemists, biophysicists, and mathematicians).

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