Driving autophagy - the role of molecular motors

Most of the vesicular transport pathways inside the cell are facilitated by molecular motors that move along cytoskeletal networks. Autophagy is a well-explored catabolic pathway that is initiated by the formation of an isolation membrane known as the phagophore, which expands to form a double-membraned structure that captures its cargo and eventually moves towards the lysosomes for fusion. Molecular motors and cytoskeletal elements have been suggested to participate at different stages of the process as the autophagic vesicles move along cytoskeletal tracks. Dynein and kinesins govern autophagosome trafficking on microtubules through the sequential recruitment of their effector proteins, post-translational modifications and interactions with LC3-interacting regions (LIRs). In contrast, myosins are actin-based motors that participate in various stages of the autophagic flux, as well as in selective autophagy pathways. However, several outstanding questions remain with regard to how the dominance of a particular motor protein over another is controlled, and to the molecular mechanisms that underlie specific disease variants in motor proteins. In this Review, we aim to provide an overview of the role of molecular motors in autophagic flux, as well as highlight their dysregulation in diseases, such as neurodegenerative disorders and pathogenic infections, and ageing.