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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivative Works 3.0 Unported License.-- et al.Brain function requires neuronal activity-dependent energy consumption. Neuronal energy supply is controlled by molecular mechanisms that regulate mitochondrial dynamics, including Kinesin motors and Mitofusins, Miro1-2 and Trak2 proteins. Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. This family of proteins is encoded by an array of armadillo (Arm) repeat-containing genes located on the X chromosome. The Armcx cluster is unique to Eutherian mammals and evolved from a single ancestor gene (Armc10). We show that these genes are highly expressed in the developing and adult nervous system. Furthermore, we demonstrate that Armcx3 expression levels regulate mitochondrial dynamics and trafficking in neurons, and that Alex3 interacts with the Kinesin/Miro/Trak2 complex in a Ca 2+ -dependent manner. Our data provide evidence of a new Eutherian-specific family of mitochondrial proteins that controls mitochondrial dynamics and indicate that this key process is differentially regulated in the brain of higher vertebrates. © 2012 Macmillan Publishers Limited. All rights reserved.This project was supported by grant BFU2008-3980 (Ministerio de Ciencia e Innovación (MICINN), Spain) and grants from the 'Marató de TV3' and 'Caixa Catalunya-Obra Social' Foundations to E. S., by grant BFU2011-23921 (MICINN) and the ICREA Academia Prize (Generalitat de Catalunya) to J.G.-F., by grants PI07/0715 (Fondo de Investigación Sanitaria) to F. B., by grant SAF2008-03514 to R. T. and by grants from the EU-ERA-Net program and MICINN (SAF2008-03175-E, BFU2010-17379 and Red de Terapia Celular, RD06/0010/0000) to J.G.-S. I. S. holds an IEF Postdoctoral fellowship funded by the Marie Curie FP7 'People' Programme.Peer Reviewe

The Eutherian Armcx genes regulate mitochondrial trafficking in neurons and interact with Miro and Trak2