Motor-driven transport of mitochondria in living cells

AGUSTINA B. FERNÁNDEZ CASAFUZ; MARIA CECILIA DE ROSSI; LUCIANA BRUNO

Conferencia; 5th International Conference on Physics and Biological Systems 2021; 2021

CONFERENCIA VIRTUALMitochondria are fundamental organelles for the correct function of eukaryotic cells. Several studies show that mitochondria are transported preferentially to areas with high metabolic demand. In order to achieve their precise location, mitochondria undergo bidirectional transport along cytoskeleton filaments driven by molecular motors, which are also relevant in regulation of mitochondria shape and size. It is well documented that mitochondrial dysfunction and changes in mitochondrial dynamics and mobility are involved in the pathology of some major neurodegenerative and neurological disorders, thus the need of understanding the underlying mechanisms in mitochondrial transport.In recent studies in X. laevis melanophore cells we have observed that mitochondria change their shape to rod-like when being transported along microtubules and that they change their length in correlation with the direction of motion: Mitochondria tend to retract during anterograde transport performed by dynein motors, whilst they maintain their length in retrograde transport mediated by kinesin motors. We also observed that slow mitochondria preferably stretch when moving.In order to explain these effects we proposed a novel one-dimensional extended model for intracellular transport of smooth flexible organelles based on a Langevin equation of motion in the overdamped limit. We ran numerical simulations to study the behavior of the cargo for different motor teams in competitive and noncompetitive scenarios, focusing on the transport properties observable in the experiments, e.g. cargo speed and length. Our results suggested that active motors adopt opposite configurations depending on the resisting load: For low loads motors push the cargo and the organelle contracts, while when the resisting load is large (e.g., in very competitive tug-of-war), motors pull the cargo and the organelle stretches. With these results we interpret the complex behavior of mitochondria transport observed in X. laevis cells.