PhD defence B. (Beatrice) Corci

The complexity of intracellular motion in mammalian cells: a study on mitochondria

Understanding how organelles move and distribute inside living cells is a crucial step to fully comprehend cell behaviour and elucidate the mechanisms of various diseases, potentially leading to new therapeutic targets. However, intracellular motion is highly complex due to the interplay of multiple factors and different regulatory mechanisms, making it challenging to fully decipher. In this thesis, we investigated mitochondrial dynamics across various cellular models and in response to different stimuli, combining microscopy techniques with mathematical analysis, to provide a qualitative and quantitative characterization of mitochondrial motion. As organelles, mitochondria were particularly suitable for this research, as they play a vital role in numerous cellular functions and act as probe for intracellular motion.Our findings demonstrate a striking similarity of mitochondrial motion across different cells. We propose this stems from mitochondria often remaining stationary for extended periods of time before moving longer distances. Alteration of various factors involved in intracellular motion affect mitochondrial motion in different ways but especially influences the waiting time before mitochondria move longer. Additionally, our research on complex-shaped cells, like neurons, highlights the role of cell structure in shaping organelle movement.Overall, this research enhances the current knowledge of mitochondrial transport but also raises important questions for future research, encouraging further exploration into the mechanisms controlling intracellular dynamics and their implications for health and diseases.