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Metaxins are core components of mitochondrial transport adaptor complexes

Author

Listed:
  • Yinsuo Zhao

    (National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Eli Song

    (National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Wenjuan Wang

    (National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Chung-Han Hsieh

    (Stanford University School of Medicine, Stanford, CA)

  • Xinnan Wang

    (Stanford University School of Medicine, Stanford, CA)

  • Wei Feng

    (National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xiangming Wang

    (National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Kang Shen

    (Stanford University)

Abstract

Trafficking of mitochondria into dendrites and axons plays an important role in the physiology and pathophysiology of neurons. Mitochondrial outer membrane protein Miro and adaptor proteins TRAKs/Milton link mitochondria to molecular motors. Here we show that metaxins MTX-1 and MTX-2 contribute to mitochondrial transport into both dendrites and axons of C. elegans neurons. MTX1/2 bind to MIRO-1 and kinesin light chain KLC-1, forming a complex to mediate kinesin-1-based movement of mitochondria, in which MTX-1/2 are essential and MIRO-1 plays an accessory role. We find that MTX-2, MIRO-1, and TRAK-1 form another distinct adaptor complex to mediate dynein-based transport. Additionally, we show that failure of mitochondrial trafficking in dendrites causes age-dependent dendrite degeneration. We propose that MTX-2 and MIRO-1 form the adaptor core for both motors, while MTX-1 and TRAK-1 specify each complex for kinesin-1 and dynein, respectively. MTX-1 and MTX-2 are also required for mitochondrial transport in human neurons, indicative of their evolutionarily conserved function.

Suggested Citation

  • Yinsuo Zhao & Eli Song & Wenjuan Wang & Chung-Han Hsieh & Xinnan Wang & Wei Feng & Xiangming Wang & Kang Shen, 2021. "Metaxins are core components of mitochondrial transport adaptor complexes," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20346-2
    DOI: 10.1038/s41467-020-20346-2
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