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

Di Meo, D; Ravindran, P; Sadhanasatish, T; Dhumale, P.; Püschel, AW

Forschungsartikel (Zeitschrift) | Peer reviewed

Zusammenfassung

Neurons are highly polarized cells that display characteristic differences in the organization of their organelles in axons and dendrites. 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 specific dynamics of axonal mitochondria. 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. SadA/B-deficient neurons show an accumulation of hyper-fused mitochondria and activation of the integrated stress response (ISR). The normal dynamics of axonal mitochondria could be restored by mild actin destabilization. Thus, the elongation after loss of SadA/B results from an excessive stabilization of actin filaments and reduction of Drp1 recruitment to mitochondria.

Details zur Publikation

FachzeitschriftCell Reports
Jahrgang / Bandnr. / Volume37
Artikelnummer110141
StatusVeröffentlicht
Veröffentlichungsjahr2021
DOI10.1016/j.celrep.2021.110141
StichwörterAnkyrin; Brsk1; Brsk2; Drp1; F-actin; Mapt; hyperfusion; mitochondrial dynamics; mitochondrial fission; neuronal polarity

Autor*innen der Universität Münster

Dhumale, Pratibha
Professur für Molekulare Zellbiologie (Prof. Püschel)
Di Meo, Danila
Professur für Molekulare Zellbiologie (Prof. Püschel)
Püschel, Andreas
Professur für Molekulare Zellbiologie (Prof. Püschel)
Ravindran, Priyadarshini
Professur für Molekulare Zellbiologie (Prof. Püschel)
Sadhanasatish, Tanmay
Professur für Quantitative Zellbiologie (Prof. Grashoff)