Fig. 2

Microtubule (MT)-mediated axonal commute of mitochondria. The ‘plus’ end-directed anterograde transport of mitochondria is mediated by kinesin-1 motor protein, which is attached to the Miro1-Milton/TRAK adaptor complex. The rhythmic walking of its motor heads over MTs is driven by the hydrolysis of ATP molecules. Deacetylation of Miro1 by HDAC6 renders it functionally inactive, and HDAC6 inhibitors such as tubastatin A reverse it. Mutations in RHOT1/2 (encoding Miro proteins) and deregulated Miro and PINK1 interactions are observed in PD pathogenesis. Various adaptors of the anterograde transport of mitochondria include syntabulin, FEZ1, RANBP2 (RAN-binding protein 2), METAXINS1/2 and Disc-1 (Disrupted in schizophrenia 1). Retrograde/ ‘minus’-end transport is facilitated by the dynein-dynactin-BICD2 complex. MTX1/MTX2/Miro1 promotes the retrograde movement of mitochondria, while MTX1/MTX2/TRAK2 promotes kinsein-1-mediated movement. The putative enhancers of mitochondrial retrograde signaling include BICD2, Snapin, Miro1, Lis1 and NDEL1. VCP downregulation observed in PD patients is a negative regulator of mitochondrial retrograde signaling. Both kinesins and dynein motor proteins responsible for axonal commute of various substances including vital organelles such as the mitochondria, seem to be dysregulated in neurodegenerative conditions such as PD