From data to model: Mitochondrial transport in living cells

BRUNO, LUCIANA; DE ROSSI, M. C.; FERNÁNDEZ CASAFUZ, AGUSTINA

Congreso; 1st Latin American Congress of Women in Bioinformatics & Data Science LA; 2020

Mitochondria are fundamental organelles for the correct function of eukaryotic cells. Severalstudies show that mitochondria are transported preferentially to areas with high metabolicdemand. In order to achieve their precise location, mitochondria undergo bidirectionaltransport along cytoskeleton filaments driven by molecular motors, which are also relevant inregulation of mitochondria shape and size. It is well documented that mitochondrialdysfunction and changes in mitochondrial dynamics and mobility are involved in thepathology of some major neurodegenerative and neurological disorders, thus the need ofunderstanding the underlying mechanisms in mitochondrial transport.In recent studies in X. laevis melanophore cells we have observed that mitochondria changetheir shape to rod-like when being transported along microtubules and that they change theirlength in correlation with the direction of motion: Mitochondria tend to retract duringanterograde transport performed by dynein motors, whilst they maintain their length inretrograde transport mediated by kinesin motors. We also observed that slow mitochondriapreferably stretch when moving.In order to explain these effects we proposed a novel one-dimensional extended model forintracellular transport of smooth flexible organelles based on a Langevin equation of motionin the overdamped limit. We ran numerical simulations to study the behavior of the cargo fordifferent motor teams in competitive and noncompetitive scenarios, focusing on the transportproperties observable in the experiments, e.g. cargo speed and length. Our resultssuggested 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 resistingload is large (e.g., in very competitive tug-of-war), motors pull the cargo and the organellestretches. With these results we interpret the complex behavior of mitochondria transportobserved in X. laevis cells.