Translational Control of Mitochondrial Energy Production Mediates Neuron Morphogenesis

SummaryMitochondrial energy production is a tightly regulated process involving the coordinated transcription of several genes, catalysis of a plethora of posttranslational modifications, and the formation of very large molecular supercomplexes. The regulation of mitochondrial activity is particularly important for the brain, which is a high-energy-consuming organ that depends on oxidative phosphorylation to generate ATP. Here we show that brain mitochondrial ATP production is controlled by the cytoplasmic polyadenylation-induced translation of an mRNA encoding NDUFV2, a key mitochondrial protein. Knockout mice lacking the Cytoplasmic Polyadenylation Element Binding protein 1 (CPEB1) have brain-specific dysfunctional mitochondria and reduced ATP levels, which is due to defective polyadenylation-induced translation of electron transport chain complex I protein NDUFV2 mRNA. This reduced ATP results in defective dendrite morphogenesis of hippocampal neurons both in vitro and in vivo. These and other results demonstrate that CPEB1 control of mitochondrial activity is essential for normal brain development.

► Cytoplasmic polyadenylation protein CPEB1 controls mitochondrial function in brain ► CPEB1 controls translation of NDUFV2 mRNA and complex I activity ► Reduced ATP in CPEB1 KO neurons impairs dendrite branching in vitro and in vivo ► NDUFV2 increases dendritic branching in CPEB1 deficient neurons in vitro and in vivo