Abstract
Mitochondria are organised as tubular networks in the cell and undergo fission and fusion. Equilibrium between the fission and fusion events is necessary to maintain normal mitochondrial function, with dysfunction of these dynamic processes correlated with disease states including neurodegeneration1,2, cancer3, and cardiomyopathy4. While several of the molecular players involved in mediating the dynamics of mitochondria have been identified5, the precise cellular cues that initiate fission or fusion remain unknown. In fission yeast, as in mammalian cells, mitochondrial positioning and partitioning are microtubule-mediated6,7. In interphase, fission yeast mitochondria associate with microtubule bundles that are aligned along the long axis of the cell8. Here we show that perturbation of microtubule dynamics via kinesin-like proteins is sufficient to shift the balance between fission and fusion of mitochondria and consequently, change mitochondrial morphology. Our results additionally fit with a stochastic model for partitioning of mitochondria during closed mitosis in fission yeast, with the absence of cytoplasmic microtubules providing the basis for increased mitochondrial fission. Finally, we propose a model whereby association of mitochondria with microtubules inhibits proper assembly of the dynamin GTPase-related fission protein Dnm1 around mitochondria. Thus, we demonstrate a general mechanism by which mitochondrial dynamics may be dictated by the dynamics of the microtubule cytoskeleton.