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

Nat Commun. 2012 May 8;3:814. doi: 10.1038/ncomms1829.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Armadillo Domain Proteins / genetics
  • Armadillo Domain Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Evolution, Molecular*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Multigene Family
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Protein Binding
  • Protein Transport
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Armadillo Domain Proteins
  • Armcx3 protein, human
  • Carrier Proteins
  • Miro-1 protein, mouse
  • Mitochondrial Proteins
  • Nerve Tissue Proteins
  • TRAK2 protein, mouse
  • Rhot2 protein, mouse
  • rho GTP-Binding Proteins