PT - JOURNAL ARTICLE AU - Valeria Ulisse AU - Swagata Dey AU - Deborah E Rothbard AU - Einav Zeevi AU - Irena Gokhman AU - Tali Dadosh AU - Adi Minis AU - Avraham Yaron TI - Regulation of axonal morphogenesis by the mitochondrial protein Efhd1 AID - 10.26508/lsa.202000753 DP - 2020 Jul 01 TA - Life Science Alliance PG - e202000753 VI - 3 IP - 7 4099 - https://www.life-science-alliance.org/content/3/7/e202000753.short 4100 - https://www.life-science-alliance.org/content/3/7/e202000753.full SO - Life Sci. Alliance2020 Jul 01; 3 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.