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bioRxiv · 10.1101/2021.07.18.452621

The balance of mitochondrial fission and fusion in cortical axons depends on the kinases SadA and SadB

Di Meo, D.·Ravindran, P.·Dhumale, P.·Puschel, A. W.
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Abstract

Neurons are highly polarized cells that display characteristic differences in the organization of their organelles in axons and dendrites. Mitochondria are of particular importance for neuronal homeostasis due to their high metabolic demand. The kinases SadA and SadB (SadA/B) promote the formation of distinct axonal and dendritic extensions during the development of cortical and hippocampal neurons. Here, we show that SadA/B are required for the axon-specific dynamics of mitochondria. The interaction with Ankyrin B (AnkB) stimulates the activity of SadA/B that function as regulators of mitochondrial dynamics through the phosphorylation of Tau. Suppression of SadA/B or AnkB in cortical neurons induces the elongation of mitochondria by disrupting the balance of fission and fusion. The normal dynamics of axonal mitochondria could be restored by mild actin destabilization. Thus, the elongation after a loss of SadA/B results from an excessive stabilization of actin filaments and reduction of Drp1 recruitment to mitochondria.

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Di Meo, D., Ravindran, P., Dhumale, P., Puschel, A. W.. 2021-07-19. The balance of mitochondrial fission and fusion in cortical axons depends on the kinases SadA and SadB. https://doi.org/10.1101/2021.07.18.452621

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