Regulation of axonal morphogenesis by the mitochondrial protein Efhd1.

ABSTRACT: 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,

SUBMITTER: Ulisse V 

PROVIDER: S-EPMC7232985 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature