How Membrane Organisation and Shape of Organelles Regulates Function?

Mitochondria are central to cell function, and their dysfunction contributes to many human diseases. Yet most assays still rely on bulk bioenergetic measurements. I will present my work using new optical tools and imaging approaches to reveal novel regulators of mitochondrial function. In particular, I will discuss how we integrated fluorescence lifetime measurements with customised environment-sensitive probes to discover (1) that cells actively adjust the fluidity of the mitochondrial inner membrane (IMM) in response to changes in respiratory demand. Separately (2), we demonstrated that mitochondria can exhibit vastly different organelle networks independent of respiratory activity, and showed that cellular ROS – as a function of metabolic state - reversibly regulates mitochondrial morphology. These findings place membrane organisation and redox-driven shape transitions at the core of mitochondrial homeostasis. I will discuss how next-generation FLIM approaches can map membrane organisation across organelles and link it to cell physiology in diverse contexts.