HDAC6 and Miro1: Another interaction causing trouble in neurons

Abstract

Myelin-associated glycoprotein and chondroitin sulfate proteoglycans in the extracellular matrix can prevent regeneration of injured axons. In this issue, Kalinski et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201702187) report that inhibition of HDAC6 prevents the deacetylation of Miro1, increases mitochondrial axonal transport, and restores the size of axonal growth cones.

Figure 1.

Schematic illustration of the interaction between HDAC6 and Miro1. Nonpermissive substrates like MAG and CSPGs activate RhoA/ROCK, increase intracellular calcium, and induce the deacetylation of Miro1 at lysine 105 (K105). This decreases mitochondrial axonal transport and inhibits the outgrowth of the axonal growth cone. Selective inhibition of the deacetylase activity of HDAC6 using tubastatin A restores axonal transport, as well as all the other phenotypes. While the interaction with kinesin-1 is responsible for anterograde transport of the mitochondria, a similar mechanism might also be present for the retrograde transport machinery.