Also, dysfunctional mitochondria are retrogradely transported towards the cell body to undergo repair, a process that occurs by fusion with healthy mitochondria or degradation by mitophagy. Thus, an increase in stationary mitochondria may result in the lack of all, or some, of these functions. Moreover, mitochondrial pausing has been related to enhanced neurotransmission and Ca2 + elevations, thereby supplying the energy required for local excitability events. Here we demonstrate that the expression of GSK3b facilitates the movement of mitochondria. On the basis of this observation, we propose that GSK3 levels and activity modulate some of the crucial events mentioned above, as previously demonstrated. Moreover, it is well known that MAPs like tau protein share and compete with microtubule motors for the same binding sites to microtubules. Indeed, we found that GSK3b overexpression results in an increase in tau phosphorylation and a decrease of tau bound to microtubules. We also observed some differences in anterograde and retrograde rates when GSK3b activity was decreased with the DN-GSK3 construct, which also acts as a dominant negative. In this way, it has recently been demonstrated that mitochondrial axonal transport is specifically inhibited by treatment with the GSK3 inhibitor lithium. There are several possible explanations for these findings. Tau L-Ascorbyl 6-palmitate interferes with the binding of motor proteins, like kinesin, to microtubules and there is a gradient of tau along the axon, with the highest levels found at the distal part of the axon, which could explain the detachment of kinesin close to the synapses. This observation might explain the fall in anterograde velocity observed when GSK3b activity decreased. Moreover, Tau protein not only competes with molecular motors for binding to microtubules but it has also been suggested that tau inhibits kinesin activity, through a mechanism Estradiol Cypionate involving tau phosphorylation. A similar gradient has been found for GSK3-phosphorylated MAP1B. Although the functional consequences of this phosphorylation are unknown, some modes of phosphorylation may favor the binding of MAP1B to microtubules. Furthermore, a higher competition of MAP1B with dynein for microtubule binding sites has been proposed. Thus, the alterations in retrograde mitochondrial transport reported here could be mediated by changes in the phosphorylation of MAP1B induced by GSK3b. In summary, here we have shown that GSK3b activity participates in the relief mitochondrial pausing, and that this relief depends largely on Tau proteins. In addition, we demonstrate that an increase in GSK3 activity results in differences in trafficking velocities of axonal mitochondria, which we propose to be dependent on both Tau and other MAP proteins.