RT Journal Article
SR Electronic
T1 Regulation of axonal morphogenesis by the mitochondrial protein Efhd1
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000753
DO 10.26508/lsa.202000753
VO 3
IS 7
A1 Ulisse, Valeria
A1 Dey, Swagata
A1 Rothbard, Deborah E
A1 Zeevi, Einav
A1 Gokhman, Irena
A1 Dadosh, Tali
A1 Minis, Adi
A1 Yaron, Avraham
YR 2020
UL http://www.life-science-alliance.org/content/3/7/e202000753.abstract
AB During development, neurons adjust their energy balance to meet the high demands of robust axonal growth and branching. The mechanisms that regulate this tuning are largely unknown. Here, we show that sensory neurons lacking liver kinase B1 (Lkb1), a master regulator of energy homeostasis, exhibit impaired axonal growth and branching. Biochemical analysis of these neurons revealed reduction in axonal ATP levels, whereas transcriptome analysis uncovered down-regulation of Efhd1 (EF-hand domain family member D1), a mitochondrial Ca2+-binding protein. Genetic ablation of Efhd1 in mice resulted in reduced axonal morphogenesis as well as enhanced neuronal death. Strikingly, this ablation causes mitochondrial dysfunction and a decrease in axonal ATP levels. Moreover, Efhd1 KO sensory neurons display shortened mitochondria at the axonal growth cones, activation of the AMP-activated protein kinase (AMPK)–Ulk (Unc-51–like autophagy-activating kinase 1) pathway and an increase in autophagic flux. Overall, this work uncovers a new mitochondrial regulator that is required for axonal morphogenesis.